# NM_006319.5(CDIPT):c.517C>T (p.Arg173Trp)

https://sugi.bio/variant/cdipt-p-arg173trp

## Summary

**CDIPT p.Arg173Trp (c.517C>T)** is classified **Uncertain significance** in CDIPT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-18). AlphaMissense: likely benign (0.2812); Ultra-rare (popmax 0.067%, mid).

**At a glance:** Uncertain significance · review: Single submitter · rsID rs368954184 · 1 submitter · AlphaMissense likely benign · ultra-rare (popmax 0.067%, mid)

## For patients & families {#patients}

This is a change in the CDIPT gene that is currently of uncertain significance — a definitive interpretation has not yet been established, 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 | [CDIPT](https://sugi.bio/atlas/gene/CDIPT/) |
| Protein change (HGVS p.) | p.Arg173Trp |
| Coding change (HGVS c.) | c.517C>T |
| MANE Select transcript | [NM_006319](https://www.ncbi.nlm.nih.gov/nuccore/NM_006319) |
| dbSNP | [rs368954184](https://www.ncbi.nlm.nih.gov/snp/rs368954184/) |
| Variant type | single nucleotide variant |
| Location | chr16:29859314-29859314 (GRCh38) |
| ClinVar | [VCV2378423](https://www.ncbi.nlm.nih.gov/clinvar/variation/2378423/) |

**All HGVS expressions:** `NC_000016.10:g.29859314G>A`, `NC_000016.9:g.29870635G>A`, `NM_001286585.2:c.382C>T`, `NM_001286586.2:c.322C>T`, `NM_006319.5:c.517C>T`

## Computational & population evidence {#evidence}

**Concordance:** ClinVar classifies this **uncertain**; the computational predictors unanimously lean **tolerated** — a triage signal, not a reclassification.

- AlphaMissense **likely benign** (0.2812)
- REVEL 0.215 (benign-leaning) — agrees with AlphaMissense
- SaProt LLR -8.679 (tolerated) — agrees with AlphaMissense
- → **In-silico consensus:** AlphaMissense, REVEL and SaProt all call this tolerated
- Conservation: phyloP 10.026, GERP 0.481, phastCons 1 — highly conserved (differs from AlphaMissense)
- CADD: **PHRED 27.9**. 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.*
- Regional missense constraint: **o/e 0.89** across the covering region of the MANE Select transcript (29,859,192–29,862,857), spanning 3,665 bp. Chi-square p 0.068. Describes the region, not this allele; gnomAD v4.1.1's own constrained determination. *Descriptive; no ACMG code applied.*
- SpliceAI: **below the reporting threshold**. This position is scored for a different substitution (G>T, Δ0.25 acceptor gain), so this allele was evaluated and its deltas all fell under Δ0.2 — a prediction of no splicing effect for this allele, not a gap in our data. *No ACMG code assigned.*
- Population frequency (gnomAD v4.1): grpmax **0.067%** (mid) · FAF95 0.0229% · FAF99 0.0138% · 4/5,968 in the highest group · 71/1,566,592 alleles overall — ultra-rare (popmax 0.067%, mid).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| Middle Eastern (grpmax) | 0.067% | 1,492 |
| Admixed American | 0.0172% | 5,810 |
| South Asian | 0.0165% | 6,061 |
| Remaining individuals (not grpmax-eligible) | 0.0148% | 6,745 |
| European (non-Finnish) | 0.00286% | 35,017 |
| East Asian | 0.00232% | 43,114 |
| African / African-American | 0.00135% | 74,230 |

*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}

**CDIPT** population constraint: LOEUF 1.042, pLI 0.0039437, missense-Z 0.46478. *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 90.02, 71% of residues very-high.

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

*Describes the biological roles of CDIPT (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:** CDIPT's established molecular role includes CDP-diacylglycerol-inositol 3-phosphatidyltransferase activity.


### Pathways affected {#pathways}

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

| Pathway (Reactome) | Evidence |
| --- | --- |
| [Synthesis of PI](https://reactome.org/content/detail/R-HSA-1483226) | curated |

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

**Molecular function:** CDP-diacylglycerol-inositol 3-phosphatidyltransferase activity.

**Biological process:** phosphatidylinositol biosynthetic process.

## Clinical significance {#significance}

**Uncertain significance** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2024-03-18.

**Submitter consensus:** unanimous (1/1 Uncertain significance).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Ambry Genetics | Uncertain significance | criteria provided, single submitter | clinical testing | 2024-03-18 |

**Reported phenotype names (ClinVar):** not specified, AllHighlyPenetrant.

## Similar variants {#similar}

Related CDIPT variant pages (same residue, condition, or type): [CDIPT p.Ala140Ser](/variant/cdipt-p-ala140ser), [CDIPT p.Ala146Ser](/variant/cdipt-p-ala146ser), [CDIPT p.Ala206Val](/variant/cdipt-p-ala206val), [CDIPT p.Ala22Ser](/variant/cdipt-p-ala22ser), [CDIPT p.Ala48Thr](/variant/cdipt-p-ala48thr), [CDIPT p.Ala84Val](/variant/cdipt-p-ala84val), [CDIPT p.Arg115Gln](/variant/cdipt-p-arg115gln), [CDIPT p.Arg138Lys](/variant/cdipt-p-arg138lys).

### 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 2378423). 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.*