Is DTYMK p.Asp128Asn (c.382G>A) pathogenic?

DTYMK p.Asp128Asn (c.382G>A) is classified Pathogenic in DTYMK (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-04-28). AlphaMissense: likely pathogenic (0.6957); Very rare (popmax 0.00167%, amr); Associated with neurodegeneration, childhood-onset, with progressive microcephaly.

What condition is associated with DTYMK p.Asp128Asn (c.382G>A)?

DTYMK p.Asp128Asn (c.382G>A) is associated with neurodegeneration, childhood-onset, with progressive microcephaly (ClinVar).

How common is DTYMK p.Asp128Asn (c.382G>A) in the general population?

DTYMK p.Asp128Asn (c.382G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about DTYMK p.Asp128Asn (c.382G>A)?

AlphaMissense predicts likely pathogenic (score 0.6957) — an in-silico prediction, not a clinical call.

DTYMK p.Asp128Asn

c.382G>A · rs373875797 · VCV1686904

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6957 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurodegeneration, childhood-onset, with progressive microcephaly

Computational evidence

Protein change
AlphaMissense	0.6957	likely pathogenic ✓ concordant with ClinVar
REVEL	0.873	moderately pathogenic-leaning
SaProt	LLR -12.27	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.6, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 11 kb · p 0.09 · regional, not allelic
Overall
CADD	33.0	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 0.00167% Admixed American · 1/60,026 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.0013% 21/1,614,166 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0203%	4,934
Admixed Americangrpmax	0.00167%	60,026
Finnishnot grpmax-eligible	0.00156%	63,992
African / African-American	0.00133%	75,042
European (non-Finnish)	0.00102%	98,337

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp128Asn
Coding: c.382G>A
MANE Select: NM_012145
dbSNP: rs373875797
Type: single nucleotide variant
Location: chr2:241678598 (GRCh38)
Gene constraint: LOEUF 1.404 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.83 · 21 PDB
Residue 128: a UniProt-annotated variant site (in conpm; loss of catalytic activity in patient fibroblasts); 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.Pro81Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
DTYMK p.Ala99Thr Pathogenic ⚠ same condition
DTYMK p.Gln89_Gly90del Likely pathogenic ★ same condition
DTYMK p.Asp96fs Pathogenic same condition
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

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-asp128asn (accessed [today's date]).

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