Is DSTYK p.Leu64Phe (c.190C>T) pathogenic?

DSTYK p.Leu64Phe (c.190C>T) is classified Benign/Likely benign in DSTYK (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0606); Common (popmax 6.24%, eas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DSTYK p.Leu64Phe (c.190C>T)?

AlphaMissense predicts likely benign (score 0.0606) — an in-silico prediction, not a clinical call.

DSTYK p.Leu64Phe

Q: How common is DSTYK p.Leu64Phe (c.190C>T) in the general population?

DSTYK p.Leu64Phe (c.190C>T) is common (popmax 6.24%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.190C>T · rs78212113 · VCV1271124

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0606 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.24%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0606	likely benign
REVEL	0.162	moderately benign-leaning
SaProt	LLR -7.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Regional constraint	o/e 1.40	unconstrained · MANE · 240 bp · p 1.2e-05 · regional, not allelic
Overall
CADD	19.01	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 6.24% East Asian · 2,792/44,770 alleles

Filtering AF 6.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.96%

Overall 2.08% 33,477/1,612,030 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	6.24%	16
South Asian	3.97%	25
Middle Eastern	3.85%	26
Ashkenazi Jewishnot grpmax-eligible	2.98%	34
Finnishnot grpmax-eligible	2.98%	34
African / African-American	2.94%	34
Admixed American	2.68%	37
Remaining individualsnot grpmax-eligible	2.62%	38
European (non-Finnish)	1.58%	63
Amishnot grpmax-eligible	0.768%	130

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.Leu64Phe
Coding: c.190C>T
MANE Select: NM_015375
dbSNP: rs78212113
Type: single nucleotide variant
Location: chr1:205211346 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.02
Residue 64: 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.Leu64= 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-leu64phe (accessed [today's date]).

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