Is DTYMK p.Val193Met (c.577G>A) pathogenic?

DTYMK p.Val193Met (c.577G>A) is classified Uncertain significance in DTYMK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.1136); Ultra-rare (popmax 0.01%, nfe).

How common is DTYMK p.Val193Met (c.577G>A) in the general population?

DTYMK p.Val193Met (c.577G>A) is ultra-rare (popmax 0.01%, nfe) (gnomAD).

What do computational predictors say about DTYMK p.Val193Met (c.577G>A)?

AlphaMissense predicts likely benign (score 0.1136) — an in-silico prediction, not a clinical call.

DTYMK p.Val193Met

c.577G>A · VCV4662420

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1136 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1136	likely benign
REVEL	0.319	indeterminate
SaProt	LLR -6.75	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3	GERP -3.5
Regional constraint	o/e 1.10	unconstrained · MANE · 11 kb · p 0.09 · regional, not allelic
Overall
CADD	1.265	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 0.01% European (non-Finnish) · 118/1,179,820 alleles

Filtering AF 0.00851% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00795%

Overall 0.008% 129/1,613,270 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.01%	9,999
African / African-American	0.00533%	18,758
East Asian	0.00446%	22,424
Admixed American	0.00333%	29,998
South Asian	0.0022%	45,489
Remaining individualsnot grpmax-eligible	0.0016%	62,470

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: DTYMK
Protein: p.Val193Met
Coding: c.577G>A
MANE Select: NM_012145
Type: single nucleotide variant
Location: chr2:241676189 (GRCh38)
Gene constraint: LOEUF 1.404 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.83 · 21 PDB
Residue 193: an α-helix

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

Similar variants

DTYMK p.Val193Gly Uncertain significance ★ ⚠ same residue
DTYMK p.Pro81Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
DTYMK p.His35Tyr Benign ★★ same type
DTYMK p.Ala104Val Uncertain significance ★ ⚠ same type
DTYMK p.Ala145Thr Uncertain significance ★ ⚠ same type
DTYMK p.Ala198Val Uncertain significance ★ ⚠ same type
DTYMK p.Ala29Gly Uncertain significance ★ ⚠ same type
DTYMK p.Ala29Ser 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/dtymk-p-val193met (accessed [today's date]).

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