Is G6PD p.Pro396Arg (c.1187C>G) pathogenic?

G6PD p.Pro396Arg (c.1187C>G) is classified Pathogenic/Likely pathogenic in G6PD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-12). AlphaMissense: likely pathogenic (0.9918); Absent from gnomAD v4.1; Associated with anemia, nonspherocytic hemolytic, due to G6PD deficiency.

What condition is associated with G6PD p.Pro396Arg (c.1187C>G)?

G6PD p.Pro396Arg (c.1187C>G) is associated with anemia, nonspherocytic hemolytic, due to G6PD deficiency (ClinVar).

How common is G6PD p.Pro396Arg (c.1187C>G) in the general population?

G6PD p.Pro396Arg (c.1187C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about G6PD p.Pro396Arg (c.1187C>G)?

AlphaMissense predicts likely pathogenic (score 0.9918) — an in-silico prediction, not a clinical call.

G6PD p.Pro396Arg

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.1187C>G · rs1557229683 · VCV987108

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9918 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

anemia, nonspherocytic hemolytic, due to G6PD deficiency

Computational evidence

Protein change
AlphaMissense	0.9918	likely pathogenic ✓ concordant with ClinVar · top 9% in G6PD
REVEL	0.973	strongly pathogenic-leaning
SaProt	LLR -12.69	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 12	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	26.9	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

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: G6PD
Protein: p.Pro396Arg
Coding: c.1187C>G
MANE Select: NM_001360016
dbSNP: rs1557229683
Type: single nucleotide variant
Location: chrX:154532667 (GRCh38)
Structure: AlphaFold pLDDT 94.54 · 25 PDB
Residue 396: a β-strand; a UniProt-annotated variant site (in cnsha1; bari; class i)

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.Pro396Ala Pathogenic/Likely pathogenic ★★ same residue
G6PD p.Pro396Leu 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-pro396arg (accessed [today's date]).

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