Is G6PD p.Pro409= (c.1227G>A) pathogenic?

G6PD p.Pro409= (c.1227G>A) is classified Likely benign in G6PD (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-23). Very rare (popmax 0.00351%, sas); Associated with anemia, nonspherocytic hemolytic, due to G6PD deficiency.

What condition is associated with G6PD p.Pro409= (c.1227G>A)?

G6PD p.Pro409= (c.1227G>A) is associated with anemia, nonspherocytic hemolytic, due to G6PD deficiency (ClinVar).

How common is G6PD p.Pro409= (c.1227G>A) in the general population?

G6PD p.Pro409= (c.1227G>A) is very rare (popmax 0.00351%, sas) (gnomAD).

G6PD p.Pro409=

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.1227G>A · rs781879876 · VCV1146154

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00351%, sas)

Conditions

anemia, nonspherocytic hemolytic, due to G6PD deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -8	GERP -3.4
Overall
CADD	0.129	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00351% South Asian · 2/57,047 alleles

Filtering AF 0.000581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000412%

Overall 0.00124% 15/1,212,379 alleles · very rare exomes 15/1,098,208 · genomes 0/114,171 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0042%	23,828
South Asiangrpmax	0.00351%	28,524
East Asian	0.00295%	33,873
European (non-Finnish)	0.00112%	89,562

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro409=
Coding: c.1227G>A
MANE Select: NM_001360016
dbSNP: rs781879876
Type: single nucleotide variant
Location: chrX:154532627 (GRCh38)
Structure: AlphaFold pLDDT 94.54 · 25 PDB
Residue 409: a β-strand

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.Pro409Arg Pathogenic ★ same residue
G6PD p.Pro409Gln Pathogenic ★ same residue
G6PD p.Pro409Ser Pathogenic ★ 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

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-pro409 (accessed [today's date]).

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