Is DTYMK p.Arg159Trp (c.475C>T) pathogenic?

DTYMK p.Arg159Trp (c.475C>T) is classified Uncertain significance in DTYMK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). AlphaMissense: likely benign (0.2534); Very rare (popmax 0.004%, afr).

How common is DTYMK p.Arg159Trp (c.475C>T) in the general population?

DTYMK p.Arg159Trp (c.475C>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about DTYMK p.Arg159Trp (c.475C>T)?

AlphaMissense predicts likely benign (score 0.2534) — an in-silico prediction, not a clinical call.

DTYMK p.Arg159Trp

c.475C>T · rs746362712 · VCV2235855

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2534 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2534	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -15.54	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 6.8	GERP 0.47, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 11 kb · p 0.09 · regional, not allelic
Overall
CADD	25.4	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 0.004% African / African-American · 3/75,048 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.00118% 19/1,614,174 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,016
Remaining individualsnot grpmax-eligible	0.0032%	31,254
East Asian	0.00223%	44,888
South Asian	0.0011%	91,080
European (non-Finnish)	0.00102%	98,337

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.Arg159Trp
Coding: c.475C>T
MANE Select: NM_012145
dbSNP: rs746362712
Type: single nucleotide variant
Location: chr2:241678505 (GRCh38)
Gene constraint: LOEUF 1.404 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.83 · 21 PDB
Residue 159: an α-helix

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

Similar variants

DTYMK p.Arg159Gln 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-arg159trp (accessed [today's date]).

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