Is G6PC3 p.Phe43= (c.129C>T) pathogenic?

G6PC3 p.Phe43= (c.129C>T) is classified Likely benign in G6PC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-07). Very rare (popmax 6.2e-05%); Associated with autosomal recessive severe congenital neutropenia due to G6PC3 deficiency.

What condition is associated with G6PC3 p.Phe43= (c.129C>T)?

G6PC3 p.Phe43= (c.129C>T) is associated with autosomal recessive severe congenital neutropenia due to G6PC3 deficiency (ClinVar).

How common is G6PC3 p.Phe43= (c.129C>T) in the general population?

G6PC3 p.Phe43= (c.129C>T) is very rare (popmax 6.2e-05%) (gnomAD).

G6PC3 p.Phe43=

Q: How is Severe congenital neutropenia due to G6PC3 deficiency inherited?

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

c.129C>T · rs2049969299 · VCV2753468

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Conditions

autosomal recessive severe congenital neutropenia due to G6PC3 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 0.51	GERP -2.4, phastCons 1
Overall
CADD	12.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,613,688 alleles · very rare exomes 0/1,461,462 · genomes 1/152,226 · joint denominator

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: G6PC3
Protein: p.Phe43=
Coding: c.129C>T
MANE Select: NM_138387
dbSNP: rs2049969299
Type: single nucleotide variant
Location: chr17:44071094 (GRCh38)
Gene constraint: LOEUF 1.008 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.79

Full G6PC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive severe congenital neutropenia due to G6PC3 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe congenital neutropenia due to G6PC3 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

G6PC3 p.Phe43Leu Uncertain significance ★ ⚠ same residue
G6PC3 p.Arg161Gln Pathogenic/Likely pathogenic ★★ same condition
G6PC3 p.Arg161Ter Pathogenic ★★ same condition
G6PC3 p.Arg189Ter Pathogenic ★★ same condition
G6PC3 p.Arg253His Pathogenic ★★ same condition
G6PC3 p.Gln277Ter Pathogenic ★★ same condition
G6PC3 p.Gly109Ser Likely pathogenic ★★ ⚠ same condition
G6PC3 p.Gly260Arg 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/g6pc3-p-phe43 (accessed [today's date]).

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