Is DTYMK p.Arg150Cys (c.448C>T) pathogenic?

DTYMK p.Arg150Cys (c.448C>T) is classified Uncertain significance in DTYMK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: ambiguous (0.3692); Very rare (popmax 0.00549%, sas).

How common is DTYMK p.Arg150Cys (c.448C>T) in the general population?

DTYMK p.Arg150Cys (c.448C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about DTYMK p.Arg150Cys (c.448C>T)?

AlphaMissense predicts ambiguous (score 0.3692) — an in-silico prediction, not a clinical call.

DTYMK p.Arg150Cys

c.448C>T · VCV4662423

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3692 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3692	ambiguous
REVEL	0.68	pathogenic-leaning
SaProt	LLR -10.22	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 11 kb · p 0.09 · regional, not allelic
Overall
CADD	26.7	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 0.00549% South Asian · 5/91,086 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00105% 17/1,614,066 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,217
Remaining individualsnot grpmax-eligible	0.0032%	31,243
African / African-American	0.00267%	37,466
Admixed American	0.00167%	60,012
European (non-Finnish)	0.000593%	168,577

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.Arg150Cys
Coding: c.448C>T
MANE Select: NM_012145
Type: single nucleotide variant
Location: chr2:241678532 (GRCh38)
Gene constraint: LOEUF 1.404 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.83 · 21 PDB
Residue 150: the 'lid' region; an α-helix

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.Ala2Val 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-arg150cys (accessed [today's date]).

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