Is G6PD p.Val431Met (c.1291G>A) pathogenic?

G6PD p.Val431Met (c.1291G>A) is classified Conflicting classifications of pathogenicity in G6PD (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-04-13). AlphaMissense: likely benign (0.2465); Very rare (popmax 0.00434%, amr); Associated with malaria, susceptibility to.

What condition is associated with G6PD p.Val431Met (c.1291G>A)?

G6PD p.Val431Met (c.1291G>A) is associated with malaria, susceptibility to, anemia, nonspherocytic hemolytic, due to G6PD deficiency (ClinVar).

How common is G6PD p.Val431Met (c.1291G>A) in the general population?

G6PD p.Val431Met (c.1291G>A) is very rare (popmax 0.00434%, amr) (gnomAD).

What do computational predictors say about G6PD p.Val431Met (c.1291G>A)?

AlphaMissense predicts likely benign (score 0.2465) — an in-silico prediction, not a clinical call.

G6PD p.Val431Met

c.1291G>A · rs782098548 · VCV1722623

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2465 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00434%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

malaria, susceptibility to

Computational evidence

Protein change
AlphaMissense	0.2465	likely benign
REVEL	0.714	pathogenic-leaning
SaProt	LLR -8.47	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 2,424 bp · p 9.7e-16 · regional, not allelic
Overall
CADD	19.67	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00434% Admixed American · 2/46,122 alleles

Filtering AF 0.000719% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000269%

Overall 0.00033% 4/1,211,247 alleles · very rare exomes 4/1,097,553 · genomes 0/113,694 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00434%	23,061
Remaining individualsnot grpmax-eligible	0.0021%	47,626
European (non-Finnish)	0.000112%	895,159

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: G6PD
Protein: p.Val431Met
Coding: c.1291G>A
MANE Select: NM_001360016
dbSNP: rs782098548
Type: single nucleotide variant
Location: chrX:154532459 (GRCh38)
Structure: AlphaFold pLDDT 94.54 · 25 PDB
Residue 431: an α-helix

Full G6PD gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

malaria, susceptibility to — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: anemia, nonspherocytic hemolytic, due to G6PD deficiency

Similar variants

G6PD p.Val431Gly Pathogenic ★ same residue
G6PD p.Val431= Likely benign ★ same residue
G6PD p.Ala335Asp Pathogenic/Likely pathogenic ★★ ⚠ same condition
G6PD p.Ala365Thr Pathogenic ★★ ⚠ same condition
G6PD p.Ala391Val Likely pathogenic ★★ same condition
G6PD p.Ala44Thr Pathogenic ★★ ⚠ same condition
G6PD p.Ala74Gly Pathogenic/Likely pathogenic ★★ same condition
G6PD p.Arg136Cys Pathogenic/Likely pathogenic ★★ 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/g6pd-p-val431met (accessed [today's date]).

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