Is GK p.Ser83Phe (c.248C>T) pathogenic?

GK p.Ser83Phe (c.248C>T) is classified Uncertain significance in GK (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-17). AlphaMissense: likely benign (0.2576); Very rare (popmax 0.00219%, amr).

How common is GK p.Ser83Phe (c.248C>T) in the general population?

GK p.Ser83Phe (c.248C>T) is very rare (popmax 0.00219%, amr) (gnomAD).

What do computational predictors say about GK p.Ser83Phe (c.248C>T)?

AlphaMissense predicts likely benign (score 0.2576) — an in-silico prediction, not a clinical call.

GK p.Ser83Phe

c.248C>T · rs1246343210 · VCV1303393

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2576 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00219%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2576	likely benign
REVEL	0.29	benign-leaning
SaProt	LLR -8.59	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 7.5	GERP 4.8, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 75 kb · p 9.5e-39 · regional, not allelic
Overall
CADD	27.1	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

Grpmax group 0.00219% Admixed American · 1/45,687 alleles

Overall 0.000101% 1/987,172 alleles · very rare exomes 1/873,641 · genomes 0/113,531 · 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: GK
Protein: p.Ser83Phe
Coding: c.248C>T
MANE Select: NM_001205019
dbSNP: rs1246343210
Type: single nucleotide variant
Location: chrX:30668107 (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-ser83phe (accessed [today's date]).

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