Is G6PD p.Arg330Cys (c.988C>T) pathogenic?

G6PD p.Arg330Cys (c.988C>T) is classified Uncertain significance in G6PD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-01). AlphaMissense: likely benign (0.1179); Very rare (popmax 0.00435%, amr); Associated with anemia, nonspherocytic hemolytic, due to G6PD deficiency.

What condition is associated with G6PD p.Arg330Cys (c.988C>T)?

G6PD p.Arg330Cys (c.988C>T) is associated with anemia, nonspherocytic hemolytic, due to G6PD deficiency (ClinVar).

How common is G6PD p.Arg330Cys (c.988C>T) in the general population?

G6PD p.Arg330Cys (c.988C>T) is very rare (popmax 0.00435%, amr) (gnomAD).

What do computational predictors say about G6PD p.Arg330Cys (c.988C>T)?

AlphaMissense predicts likely benign (score 0.1179) — an in-silico prediction, not a clinical call.

G6PD p.Arg330Cys

Q: How is Class I glucose-6-phosphate dehydrogenase deficiency inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.988C>T · rs782699946 · VCV1722703

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1179 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00435%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

anemia, nonspherocytic hemolytic, due to G6PD deficiency

Computational evidence

Protein change
AlphaMissense	0.1179	likely benign
REVEL	0.364	indeterminate
SaProt	LLR -7.90	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 4.4	GERP -0.69, phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 2,424 bp · p 9.7e-16 · regional, not allelic
Overall
CADD	20.6	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 0.00435% Admixed American · 2/46,000 alleles

Filtering AF 0.000721% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00027%

Overall 0.000743% 9/1,210,577 alleles · very rare exomes 8/1,097,982 · genomes 1/112,595 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00435%	23,000
European (non-Finnish)	0.000782%	127,885

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.Arg330Cys
Coding: c.988C>T
MANE Select: NM_001360016
dbSNP: rs782699946
Type: single nucleotide variant
Location: chrX:154533005 (GRCh38)
Structure: AlphaFold pLDDT 94.54 · 25 PDB

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

Disease context

anemia, nonspherocytic hemolytic, due to G6PD deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Class I glucose-6-phosphate dehydrogenase deficiency (Orphanet):

Inheritance: X-linked recessive
Onset: Neonatal
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

G6PD p.Arg330= Likely benign ★★ same residue
G6PD p.Arg330His Conflicting classifications of pathogenicity ★ ⚠ 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-arg330cys (accessed [today's date]).

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