Is DTYMK p.Arg200His (c.599G>A) pathogenic?

DTYMK p.Arg200His (c.599G>A) is classified Uncertain significance in DTYMK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). AlphaMissense: likely benign (0.0854); Ultra-rare (popmax 0.0337%, mid).

How common is DTYMK p.Arg200His (c.599G>A) in the general population?

DTYMK p.Arg200His (c.599G>A) is ultra-rare (popmax 0.0337%, mid) (gnomAD).

What do computational predictors say about DTYMK p.Arg200His (c.599G>A)?

AlphaMissense predicts likely benign (score 0.0854) — an in-silico prediction, not a clinical call.

DTYMK p.Arg200His

c.599G>A · VCV4245331

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0854 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0337%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0854	likely benign
REVEL	0.352	indeterminate
SaProt	LLR -9.18	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.6	GERP -3.5
Regional constraint	o/e 1.10	unconstrained · MANE · 11 kb · p 0.09 · regional, not allelic
Overall
CADD	0.013	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0337% Middle Eastern · 2/5,938 alleles

Filtering AF 0.00814% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0066%

Overall 0.00732% 118/1,612,856 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0337%	2,969
African / African-American	0.0147%	6,820
European (non-Finnish)	0.00848%	11,795
Remaining individualsnot grpmax-eligible	0.0064%	15,615
East Asian	0.00223%	44,822

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.Arg200His
Coding: c.599G>A
MANE Select: NM_012145
Type: single nucleotide variant
Location: chr2:241676167 (GRCh38)
Gene constraint: LOEUF 1.404 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.83 · 21 PDB
Residue 200: an α-helix

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

Similar variants

DTYMK p.Arg200Cys 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-arg200his (accessed [today's date]).

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