Is DTYMK p.Asp96fs (c.287_320del) pathogenic?

DTYMK p.Asp96fs (c.287320del) is classified Pathogenic in DTYMK (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-04-28). Very rare (popmax 0.00223%, eas); Associated with neurodegeneration, childhood-onset, with progressive microcephaly.

What condition is associated with DTYMK p.Asp96fs (c.287_320del)?

DTYMK p.Asp96fs (c.287_320del) is associated with neurodegeneration, childhood-onset, with progressive microcephaly (ClinVar).

How common is DTYMK p.Asp96fs (c.287_320del) in the general population?

DTYMK p.Asp96fs (c.287_320del) is very rare (popmax 0.00223%, eas) (gnomAD).

DTYMK p.Asp96fs

c.287_320del · rs1005167119 · VCV1686902

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

neurodegeneration, childhood-onset, with progressive microcephaly

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -6.6	GERP -3.4

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,882 alleles

Overall 6.84e-05% 1/1,461,838 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.Asp96fs
Coding: c.287_320del
MANE Select: NM_012145
dbSNP: rs1005167119
Type: Deletion
Location: chr2:241680239 (GRCh38)
Gene constraint: LOEUF 1.404 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.83 · 21 PDB
Residue 96: a β-strand

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

Disease context

neurodegeneration, childhood-onset, with progressive microcephaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DTYMK p.Gln89_Gly90del Likely pathogenic ★ same condition
DTYMK p.Pro81Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
DTYMK p.Ala99Thr Pathogenic ⚠ same condition
DTYMK p.Asp128Asn Pathogenic same condition

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-asp96fs (accessed [today's date]).

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