Is DTYMK p.Pro43Leu (c.128C>T) pathogenic?

DTYMK p.Pro43Leu (c.128C>T) is classified Uncertain significance in DTYMK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-07). AlphaMissense: likely pathogenic (0.9419); Very rare (popmax 0.00122%, sas).

How common is DTYMK p.Pro43Leu (c.128C>T) in the general population?

DTYMK p.Pro43Leu (c.128C>T) is very rare (popmax 0.00122%, sas) (gnomAD).

What do computational predictors say about DTYMK p.Pro43Leu (c.128C>T)?

AlphaMissense predicts likely pathogenic (score 0.9419) — an in-silico prediction, not a clinical call.

DTYMK p.Pro43Leu

c.128C>T · VCV4015267

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9419 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00122%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9419	likely pathogenic
REVEL	0.466	indeterminate
SaProt	LLR -14.95	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.2, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 11 kb · p 0.09 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00122% South Asian · 1/82,010 alleles

Filtering AF 0.00037% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000268%

Overall 0.000734% 10/1,362,884 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00122%	82,010
European (non-Finnish)	0.000787%	127,059

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.Pro43Leu
Coding: c.128C>T
MANE Select: NM_012145
Type: single nucleotide variant
Location: chr2:241686656 (GRCh38)
Gene constraint: LOEUF 1.404 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.83 · 21 PDB
Residue 43: a β-strand

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-pro43leu (accessed [today's date]).

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