Is GAPDH p.Arg118Ser (c.354G>T) pathogenic?

GAPDH p.Arg118Ser (c.354G>T) is classified Uncertain significance in GAPDH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-14). AlphaMissense: likely pathogenic (0.9714); Absent from gnomAD v4.1.

How common is GAPDH p.Arg118Ser (c.354G>T) in the general population?

GAPDH p.Arg118Ser (c.354G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GAPDH p.Arg118Ser (c.354G>T)?

AlphaMissense predicts likely pathogenic (score 0.9714) — an in-silico prediction, not a clinical call.

GAPDH p.Arg118Ser

c.354G>T · rs2540154116 · VCV3098309

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9714 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9714	likely pathogenic
REVEL	0.384	indeterminate
SaProt	LLR -14.42	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -2.1, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 3,334 bp · p 9.1e-12 · regional, not allelic
Overall
CADD	24.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GAPDH
Protein: p.Arg118Ser
Coding: c.354G>T
MANE Select: NM_002046
dbSNP: rs2540154116
Type: single nucleotide variant
Location: chr12:6537127 (GRCh38)
Gene constraint: LOEUF 0.679 · pLI 0.19 (gnomAD)
Structure: AlphaFold pLDDT 98.17 · 23 PDB
Residue 118: 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.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
GAPDH p.Lys334Gln 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-arg118ser (accessed [today's date]).

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