Is GK p.Cys72Arg (c.214T>C) pathogenic?

GK p.Cys72Arg (c.214T>C) is classified Uncertain significance in GK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-24). AlphaMissense: likely pathogenic (0.5862); Absent from gnomAD v4.1.

How common is GK p.Cys72Arg (c.214T>C) in the general population?

GK p.Cys72Arg (c.214T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GK p.Cys72Arg (c.214T>C)?

AlphaMissense predicts likely pathogenic (score 0.5862) — an in-silico prediction, not a clinical call.

GK p.Cys72Arg

c.214T>C · VCV3392722

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5862 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,122,478)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5862	likely pathogenic
REVEL	0.577	indeterminate
SaProt	LLR -8.98	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.80 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 4.8, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 75 kb · p 9.5e-39 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,122,478). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GK
Protein: p.Cys72Arg
Coding: c.214T>C
MANE Select: NM_001205019
Type: single nucleotide variant
Location: chrX:30668073 (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-cys72arg (accessed [today's date]).

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