Is DSTYK p.Gly71Ser (c.211G>A) pathogenic?

DSTYK p.Gly71Ser (c.211G>A) is classified Conflicting classifications of pathogenicity in DSTYK (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-28). AlphaMissense: likely benign (0.0789); Rare (popmax 0.201%, afr).

How common is DSTYK p.Gly71Ser (c.211G>A) in the general population?

DSTYK p.Gly71Ser (c.211G>A) is rare (popmax 0.201%, afr) (gnomAD).

What do computational predictors say about DSTYK p.Gly71Ser (c.211G>A)?

AlphaMissense predicts likely benign (score 0.0789) — an in-silico prediction, not a clinical call.

DSTYK p.Gly71Ser

c.211G>A · rs113488459 · VCV2067640

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0789 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.201%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0789	likely benign
REVEL	0.181	moderately benign-leaning
SaProt	LLR -6.56	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 -0.15	GERP 2.2, phastCons 0.031
Regional constraint	o/e 1.40	unconstrained · MANE · 240 bp · p 1.2e-05 · regional, not allelic
Overall
CADD	15.7	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

Grpmax group 0.201% African / African-American · 150/74,790 alleles

Filtering AF 0.174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.164%

Overall 0.0116% 187/1,611,016 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.201%	499
Remaining individualsnot grpmax-eligible	0.0224%	4,455
Admixed American	0.0184%	5,440
Middle Eastern	0.0165%	6,052
South Asian	0.0011%	90,646
European (non-Finnish)	0.000848%	117,884

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: DSTYK
Protein: p.Gly71Ser
Coding: c.211G>A
MANE Select: NM_015375
dbSNP: rs113488459
Type: single nucleotide variant
Location: chr1:205211325 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 71: a UniProt-annotated variant site (in cakut1; uncertain significance)

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

Similar variants

DSTYK p.Gly71= Likely benign ★ same residue
DSTYK p.Ala206Val Uncertain significance ★★ ⚠ same type
DSTYK p.Ala477Ser Uncertain significance ★★ ⚠ same type
DSTYK p.Ala601Val Uncertain significance ★★ ⚠ same type
DSTYK p.Arg411Gln Uncertain significance ★★ ⚠ same type
DSTYK p.Arg462Gln Uncertain significance ★★ ⚠ same type
DSTYK p.Arg471Gln Uncertain significance ★★ ⚠ same type
DSTYK p.Arg626Gln Uncertain significance ★★ ⚠ 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/dstyk-p-gly71ser (accessed [today's date]).

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