Is G6PC3 p.Pro296Ser (c.886C>T) pathogenic?

G6PC3 p.Pro296Ser (c.886C>T) is classified Uncertain significance in G6PC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-06). AlphaMissense: likely benign (0.1087); Absent from gnomAD v4.1; Associated with autosomal recessive severe congenital neutropenia due to G6PC3 deficiency.

What condition is associated with G6PC3 p.Pro296Ser (c.886C>T)?

G6PC3 p.Pro296Ser (c.886C>T) is associated with autosomal recessive severe congenital neutropenia due to G6PC3 deficiency (ClinVar).

How common is G6PC3 p.Pro296Ser (c.886C>T) in the general population?

G6PC3 p.Pro296Ser (c.886C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about G6PC3 p.Pro296Ser (c.886C>T)?

AlphaMissense predicts likely benign (score 0.1087) — an in-silico prediction, not a clinical call.

G6PC3 p.Pro296Ser

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.886C>T · rs2509372591 · VCV2057204

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1087 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive severe congenital neutropenia due to G6PC3 deficiency

Computational evidence

Protein change
AlphaMissense	0.1087	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -6.66	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.27	GERP -2.7
Regional constraint	o/e 0.85	unconstrained · MANE · 5,074 bp · p 0.0017 · regional, not allelic
Overall
CADD	2.289	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

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: G6PC3
Protein: p.Pro296Ser
Coding: c.886C>T
MANE Select: NM_138387
dbSNP: rs2509372591
Type: single nucleotide variant
Location: chr17:44075888 (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.Pro296Leu Uncertain significance ★★ ⚠ same residue
G6PC3 p.Pro296= Likely benign ★ 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

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-pro296ser (accessed [today's date]).

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