# NM_024664.4(PPCS):c.88C>T (p.Leu30=)

https://sugi.bio/variant/ppcs-p-leu30

## Summary

**PPCS p.Leu30= (c.88C>T)** is classified **Likely benign** in PPCS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-12). Very rare (popmax 0.000767%, nfe).

**At a glance:** Likely benign · review: Single submitter · rsID rs1265978840 · 1 submitter · very rare (popmax 0.000767%, nfe)

## For patients & families {#patients}

This is a change in the PPCS gene that is classified as likely 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 | [PPCS](https://sugi.bio/atlas/gene/PPCS/) |
| Protein change (HGVS p.) | p.Leu30= |
| Coding change (HGVS c.) | c.88C>T |
| MANE Select transcript | [NM_001395517](https://www.ncbi.nlm.nih.gov/nuccore/NM_001395517) (variant reported on NM_024664) |
| dbSNP | [rs1265978840](https://www.ncbi.nlm.nih.gov/snp/rs1265978840/) |
| Variant type | single nucleotide variant |
| Location | chr1:42456653-42456653 (GRCh38) |
| ClinVar | [VCV2055041](https://www.ncbi.nlm.nih.gov/clinvar/variation/2055041/) |

**All HGVS expressions:** `NC_000001.10:g.42922324C>T`, `NC_000001.11:g.42456653C>T`, `NG_163395.1:g.140C>T`, `NM_001077447.3:c.-12+25C>T`, `NM_001287506.1:c.-12+154C>T`, `NM_001287507.1:c.-328+154C>T`, `NM_001287508.2:c.-83C>T`, `NM_001287509.2:c.-12+70C>T`, `NM_001287510.2:c.-605C>T`, `NM_001287511.2:c.88C>T`, `NM_001355226.2:c.-984+154C>T`, `NM_024664.4:c.88C>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 (below), not from a missing predictor score.
- Conservation: phyloP 0.377, GERP -2.98, phastCons 0.029 — weakly conserved position
- CADD: **PHRED 11.28**. 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: **not looked up on this page** — it was served without the gene's SpliceAI index, so no lookup was made. This is a gap in this page, not in the data, and says nothing about whether a splicing effect is predicted.
- Population frequency (gnomAD v4.1): grpmax **0.000767%** (nfe) · FAF95 0.000361% · FAF99 0.000261% · 9/1,173,556 in the highest group · 9/1,443,760 alleles overall — very rare (popmax 0.000767%, nfe).

*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.*

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2024-10-12.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2024-10-12 |

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

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); 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 2026-07-14); 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 2055041). 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.*