Is WDPCP p.Val331Phe (c.991G>T) pathogenic?

WDPCP p.Val331Phe (c.991G>T) is classified Uncertain significance in WDPCP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-25). AlphaMissense: likely benign (0.1817); Very rare (popmax 0.000932%, nfe); Associated with Inborn genetic diseases.

What condition is associated with WDPCP p.Val331Phe (c.991G>T)?

WDPCP p.Val331Phe (c.991G>T) is associated with Inborn genetic diseases (ClinVar).

How common is WDPCP p.Val331Phe (c.991G>T) in the general population?

WDPCP p.Val331Phe (c.991G>T) is very rare (popmax 0.000932%, nfe) (gnomAD).

What do computational predictors say about WDPCP p.Val331Phe (c.991G>T)?

AlphaMissense predicts likely benign (score 0.1817) — an in-silico prediction, not a clinical call.

WDPCP p.Val331Phe

c.991G>T · rs376497851 · VCV2540498

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1817 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1817	likely benign
REVEL	0.323	indeterminate
SaProt	LLR -9.10	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.99, phastCons 0.96
Regional constraint	o/e 0.95	unconstrained · MANE · 466 kb · p 0.14 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

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

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,179,956 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,614,036 alleles · very rare exomes 11/1,461,750 · genomes 0/152,286 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: WDPCP
Protein: p.Val331Phe
Coding: c.991G>T
MANE Select: NM_015910
dbSNP: rs376497851
Type: single nucleotide variant
Location: chr2:63404492 (GRCh38)
Gene constraint: LOEUF 0.939 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.71 · 1 PDB

Full WDPCP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

WDPCP p.Gln327Ter Pathogenic/Likely pathogenic ★★ same condition
WDPCP p.Ala617Val Uncertain significance ★★ ⚠ same condition
WDPCP p.Arg201Gly Uncertain significance ★★ ⚠ same condition
WDPCP p.Arg323Gln Uncertain significance ★★ ⚠ same condition
WDPCP p.Arg368Cys Uncertain significance ★★ ⚠ same condition
WDPCP p.Arg368His Uncertain significance ★★ ⚠ same condition
WDPCP p.Asn651His Uncertain significance ★★ ⚠ same condition
WDPCP p.Asp358Asn Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/wdpcp-p-val331phe (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown