Is DTYMK p.Val63= (c.189G>A) pathogenic?

DTYMK p.Val63= (c.189G>A) is classified Likely benign in DTYMK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-01). Very rare (popmax 0.000424%, nfe).

How common is DTYMK p.Val63= (c.189G>A) in the general population?

DTYMK p.Val63= (c.189G>A) is very rare (popmax 0.000424%, nfe) (gnomAD).

DTYMK p.Val63=

c.189G>A · VCV3389084

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.064	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP -0.6, phastCons 0.96
Overall
CADD	7.296	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,028 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000342% 5/1,461,872 alleles · very rare

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.Val63=
Coding: c.189G>A
MANE Select: NM_012145
Type: single nucleotide variant
Location: chr2:241685819 (GRCh38)
Gene constraint: LOEUF 1.404 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.83 · 21 PDB

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-val63 (accessed [today's date]).

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