Is GK p.Ser91Arg (c.273C>G) pathogenic?

GK p.Ser91Arg (c.273C>G) is classified Uncertain significance in GK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-08). AlphaMissense: likely pathogenic (0.9924); Absent from gnomAD v4.1.

How common is GK p.Ser91Arg (c.273C>G) in the general population?

GK p.Ser91Arg (c.273C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GK p.Ser91Arg (c.273C>G)?

AlphaMissense predicts likely pathogenic (score 0.9924) — an in-silico prediction, not a clinical call.

GK p.Ser91Arg

c.273C>G · VCV3376108

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9924 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9924	likely pathogenic · top 5% in GK
REVEL	0.44	indeterminate
SaProt	LLR -14.14	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 75 kb · p 9.5e-39 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: GK
Protein: p.Ser91Arg
Coding: c.273C>G
MANE Select: NM_001205019
Type: single nucleotide variant
Location: chrX:30677388 (GRCh38)
Structure: AlphaFold pLDDT 92.01

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

Similar variants

GK c.152+1G>C Likely pathogenic ★★ same type
GK p.Leu36Phe Uncertain significance ★★ same type
GK p.Val168Ile Uncertain significance ★★ ⚠ same type
GK p.Val194Ile Uncertain significance ★★ ⚠ same type
GK c.1054+22G>T Benign ★★ same type
GK c.1357+20T>C Benign ★★ same type
GK c.1501+181T>C Benign ★★ same type
GK c.1669+121A>T Benign ★★ same type

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/gk-p-ser91arg (accessed [today's date]).

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