Is GK p.Ser371= (c.1113G>A) pathogenic?

GK p.Ser371= (c.1113G>A) is classified Benign/Likely benign in GK (ClinVar, Multiple submitters, 4 submitters; last evaluated 2019-12-31). Rare (popmax 0.498%, afr); Associated with Inborn genetic diseases.

What condition is associated with GK p.Ser371= (c.1113G>A)?

GK p.Ser371= (c.1113G>A) is associated with Inborn genetic diseases (ClinVar).

How common is GK p.Ser371= (c.1113G>A) in the general population?

GK p.Ser371= (c.1113G>A) is rare (popmax 0.498%, afr) (gnomAD).

GK p.Ser371=

c.1113G>A · rs139652893 · VCV590223

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.498%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -0.26	GERP 1.2, phastCons 0.001
Overall
CADD	13.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.498% African / African-American · 282/56,624 alleles

Filtering AF 0.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.432%

Overall 0.0283% 335/1,184,873 alleles · rare exomes 154/1,073,790 · genomes 181/111,083 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.498%	201
Admixed American	0.068%	1,470
Remaining individualsnot grpmax-eligible	0.0321%	3,119
Middle Eastern	0.0241%	4,155
South Asian	0.00357%	28,026
European (non-Finnish)	0.000458%	218,305

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: GK
Protein: p.Ser371=
Coding: c.1113G>A
MANE Select: NM_001205019
dbSNP: rs139652893
Type: single nucleotide variant
Location: chrX:30719477 (GRCh38)
Structure: AlphaFold pLDDT 92.01

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GK p.Val168Ile Uncertain significance ★★ ⚠ same condition
GK p.Val194Ile Uncertain significance ★★ ⚠ same condition
GK p.Gln55= Benign ★★ same condition
GK c.1151+1G>T Likely pathogenic ★ same condition
GK c.1236+2T>C Likely pathogenic ★ same condition
GK p.Ala382Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
GK p.Arg419Gln Uncertain significance ★ ⚠ same condition
GK p.Arg49Lys Uncertain significance ★ ⚠ 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/gk-p-ser371 (accessed [today's date]).

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