Is G6PD p.Phe138= (c.414C>T) pathogenic?

G6PD p.Phe138= (c.414C>T) is classified Likely benign in G6PD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-24). Ultra-rare (popmax 0.0232%, mid); Associated with anemia, nonspherocytic hemolytic, due to G6PD deficiency.

What condition is associated with G6PD p.Phe138= (c.414C>T)?

G6PD p.Phe138= (c.414C>T) is associated with anemia, nonspherocytic hemolytic, due to G6PD deficiency (ClinVar).

How common is G6PD p.Phe138= (c.414C>T) in the general population?

G6PD p.Phe138= (c.414C>T) is ultra-rare (popmax 0.0232%, mid) (gnomAD).

G6PD p.Phe138=

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.414C>T · rs2148331303 · VCV1456506

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0232%, mid)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 0.51, phastCons 1
Overall
CADD	10.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0232% Middle Eastern · 1/4,310 alleles

Overall 0.000165% 2/1,212,087 alleles · ultra-rare exomes 2/1,098,134 · genomes 0/113,953 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0232%	4,310
South Asian	0.00175%	57,019

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.Phe138=
Coding: c.414C>T
MANE Select: NM_001360016
dbSNP: rs2148331303
Type: single nucleotide variant
Location: chrX:154535239 (GRCh38)
Structure: AlphaFold pLDDT 94.54 · 25 PDB
Residue 138: 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.Phe138Val Likely 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
G6PD p.Arg136Cys Pathogenic/Likely pathogenic ★★ same condition
G6PD p.Arg166Cys 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-phe138 (accessed [today's date]).

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