Is DTYMK p.Ala2Val (c.5C>T) pathogenic?

DTYMK p.Ala2Val (c.5C>T) is classified Uncertain significance in DTYMK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-07). AlphaMissense: likely benign (0.3042); Very rare (popmax 0.00955%, nfe).

How common is DTYMK p.Ala2Val (c.5C>T) in the general population?

DTYMK p.Ala2Val (c.5C>T) is very rare (popmax 0.00955%, nfe) (gnomAD).

What do computational predictors say about DTYMK p.Ala2Val (c.5C>T)?

AlphaMissense predicts likely benign (score 0.3042) — an in-silico prediction, not a clinical call.

DTYMK p.Ala2Val

c.5C>T · rs767655288 · VCV2467037

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3042 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00955%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3042	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -10.79	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.24, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 11 kb · p 0.09 · regional, not allelic
Overall
CADD	23.4	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 0.00955% European (non-Finnish) · 107/1,120,662 alleles

Filtering AF 0.00806% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00746%

Overall 0.00753% 110/1,460,932 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00955%	10,473
Admixed American	0.00272%	36,716
Remaining individualsnot grpmax-eligible	0.00179%	55,920
African / African-American	0.00148%	67,724

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.Ala2Val
Coding: c.5C>T
MANE Select: NM_012145
dbSNP: rs767655288
Type: single nucleotide variant
Location: chr2:241686779 (GRCh38)
Gene constraint: LOEUF 1.404 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.83 · 21 PDB
Residue 2: a modified residue (n-acetylalanine)

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

Similar variants

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
DTYMK p.Ala3Val 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-ala2val (accessed [today's date]).

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