Is GAPDH p.Val119Phe (c.355G>T) pathogenic?

GAPDH p.Val119Phe (c.355G>T) is classified Uncertain significance in GAPDH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-12). AlphaMissense: likely pathogenic (0.9941); Very rare (popmax 8.47e-05%, nfe).

How common is GAPDH p.Val119Phe (c.355G>T) in the general population?

GAPDH p.Val119Phe (c.355G>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about GAPDH p.Val119Phe (c.355G>T)?

AlphaMissense predicts likely pathogenic (score 0.9941) — an in-silico prediction, not a clinical call.

GAPDH p.Val119Phe

c.355G>T · rs2540154128 · VCV2611275

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9941 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9941	likely pathogenic
REVEL	0.723	pathogenic-leaning
SaProt	LLR -14.29	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 3,334 bp · p 9.1e-12 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.47e-05% European (non-Finnish) · 1/1,179,968 alleles

Overall 6.84e-05% 1/1,461,680 alleles · very rare

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: GAPDH
Protein: p.Val119Phe
Coding: c.355G>T
MANE Select: NM_002046
dbSNP: rs2540154128
Type: single nucleotide variant
Location: chr12:6537128 (GRCh38)
Gene constraint: LOEUF 0.679 · pLI 0.19 (gnomAD)
Structure: AlphaFold pLDDT 98.17 · 23 PDB
Residue 119: the 'interaction with wars1' region; a β-strand

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

Similar variants

GAPDH c.-8C>G Benign ★★ same type
NCAPD2 c.4120+2T>C Pathogenic ★ same type
GAPDH p.Ala265Thr Uncertain significance ★ same type
GAPDH p.Arg118Ser Uncertain significance ★ ⚠ same type
GAPDH p.Arg323Lys Uncertain significance ★ ⚠ same type
GAPDH p.Asn304Ser Uncertain significance ★ ⚠ same type
GAPDH p.Asp198Gly Uncertain significance ★ ⚠ same type
GAPDH p.His165Arg Uncertain significance ★ ⚠ same type

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/gapdh-p-val119phe (accessed [today's date]).

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