# NM_139248.3(LIPH):c.51C>T (p.Asp17=)

https://sugi.bio/variant/liph-p-asp17

## Summary

**LIPH p.Asp17= (c.51C>T)** is classified **Benign** in LIPH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-02). Rare (popmax 0.74%, eas).

**At a glance:** Benign · review: Single submitter · rsID rs139264479 · 1 submitter · rare (popmax 0.74%, eas)

## For patients & families {#patients}

This is a change in the LIPH gene that is classified as benign — not considered disease-causing, submitted by 1 submitter.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [LIPH](https://sugi.bio/atlas/gene/LIPH/) |
| Protein change (HGVS p.) | p.Asp17= |
| Coding change (HGVS c.) | c.51C>T |
| MANE Select transcript | [NM_139248](https://www.ncbi.nlm.nih.gov/nuccore/NM_139248) |
| dbSNP | [rs139264479](https://www.ncbi.nlm.nih.gov/snp/rs139264479/) |
| Variant type | single nucleotide variant |
| Location | chr3:185535131-185535131 (GRCh38) |
| ClinVar | [VCV2056690](https://www.ncbi.nlm.nih.gov/clinvar/variation/2056690/) |

**All HGVS expressions:** `NC_000003.11:g.185252919G>A`, `NC_000003.12:g.185535131G>A`, `NG_012183.1:g.22451C>T`, `NM_139248.3:c.51C>T`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation and, for splice-region changes, SpliceAI (below), not from a missing predictor score.
- SpliceAI predicts **acceptor gain** (Δ 0.20) — a splice-altering prediction the current classification does not reflect
- Conservation: phyloP -0.274, GERP -3.23 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- CADD: **PHRED 8.742**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI deltas (raw): acceptor loss **0.01**, donor loss **0.00**, acceptor gain **0.20**, donor gain **0.00**. Largest is acceptor gain, 1 bp away.
- SpliceAI deltas (masked): acceptor loss **0.00**, donor loss **0.00**, acceptor gain **0.00**, donor gain **0.00**.
  Masked SpliceAI — what Ensembl VEP and the Broad lookup serve by default — is below the reporting threshold here, so those tools show **no splice signal** for this allele. Masking zeroes a loss scored against a position that is not an annotated splice site, and a gain that merely strengthens an existing one, so the raw score above is describing a cryptic site rather than the site the variant sits on. *No ACMG code is assigned either way.*
- Population frequency (gnomAD v4.1): grpmax **0.74%** (eas) · FAF95 0.674% · FAF99 0.649% · 332/44,882 in the highest group · 2,660/1,613,882 alleles overall — rare (popmax 0.74%, eas).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Finnish (not grpmax-eligible) | 2.65% | 38 |
| East Asian (grpmax) | 0.74% | 135 |
| Remaining individuals (not grpmax-eligible) | 0.163% | 613 |
| Admixed American | 0.147% | 682 |
| South Asian | 0.119% | 843 |
| Ashkenazi Jewish (not grpmax-eligible) | 0.098% | 1,021 |
| Middle Eastern | 0.066% | 1,516 |
| European (non-Finnish) | 0.0253% | 3,960 |
| African / African-American | 0.00933% | 10,715 |

Finnish shows a higher raw frequency than the grpmax group. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and "Remaining individuals" — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**LIPH** population constraint: LOEUF 0.811, pLI 0.0074261, missense-Z 0.90155. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 90.89, 80% of residues very-high.

## What this gene does {#gene-function}

*Describes the biological roles of LIPH (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** LIPH's established molecular role includes glycerophospholipase activity.


### Pathways affected {#pathways}

LIPH participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Synthesis of PA](https://reactome.org/content/detail/R-HSA-1483166) | curated |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** glycerophospholipase activity, heparin binding.

**Biological process:** lipid catabolic process.

## Clinical significance {#significance}

**Benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2024-12-02.

**Submitter consensus:** unanimous (1/1 Benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2024-12-02 |

**Reported phenotype names (ClinVar):** not provided, none provided.

## Similar variants {#similar}

Related LIPH variant pages (same residue, condition, or type): [LIPH p.Arg110Ter](/variant/liph-p-arg110ter), [LIPH p.Cys246Ser](/variant/liph-p-cys246ser), [LIPH p.His248Asn](/variant/liph-p-his248asn), [LIPH p.Ala180Gly](/variant/liph-p-ala180gly), [LIPH p.Arg110Leu](/variant/liph-p-arg110leu), [LIPH p.Ile336Met](/variant/liph-p-ile336met), [LIPH p.Thr286Met](/variant/liph-p-thr286met), [LIPH c.1094+29C>T](/variant/liph-c-1094-plus-29c-t).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-14); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 2056690). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*