Is GK p.Ser516= (c.1548A>T) pathogenic?

GK p.Ser516= (c.1548A>T) is classified Likely benign in GK (ClinVar, Single submitter, 1 submitter; last evaluated 2018-05-08). Ultra-rare (popmax 0.0531%, mid).

How common is GK p.Ser516= (c.1548A>T) in the general population?

GK p.Ser516= (c.1548A>T) is ultra-rare (popmax 0.0531%, mid) (gnomAD).

GK p.Ser516=

c.1548A>T · rs377416052 · VCV743693

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0531%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 3.7, phastCons 1
Overall
CADD	14.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0531% Middle Eastern · 2/3,763 alleles

Filtering AF 0.00939% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00229% 27/1,178,497 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0531%	1,881
Remaining individualsnot grpmax-eligible	0.0043%	23,245
European (non-Finnish)	0.00265%	37,691

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.Ser516=
Coding: c.1548A>T
MANE Select: NM_001205019
dbSNP: rs377416052
Type: single nucleotide variant
Location: chrX:30724147 (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-ser516 (accessed [today's date]).

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