Is DTX4 p.Asp82His (c.244G>C) pathogenic?

DTX4 p.Asp82His (c.244G>C) is classified Uncertain significance in DTX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: ambiguous (0.4614); Very rare (popmax 0.00223%, eas).

How common is DTX4 p.Asp82His (c.244G>C) in the general population?

DTX4 p.Asp82His (c.244G>C) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DTX4 p.Asp82His (c.244G>C)?

AlphaMissense predicts ambiguous (score 0.4614) — an in-silico prediction, not a clinical call.

DTX4 p.Asp82His

c.244G>C · VCV4015257

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4614 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4614	ambiguous
REVEL	0.211	benign-leaning
SaProt	LLR -5.32	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 32 kb · p 2.6e-05 · regional, not allelic
Overall
CADD	26.0	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 0.00223% East Asian · 1/44,878 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000682% 11/1,612,278 alleles · very rare exomes 10/1,460,152 · genomes 1/152,126 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
Remaining individualsnot grpmax-eligible	0.0016%	62,380
African / African-American	0.00134%	74,884
European (non-Finnish)	0.000679%	147,367

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: DTX4
Protein: p.Asp82His
Coding: c.244G>C
MANE Select: NM_015177
Type: single nucleotide variant
Location: chr11:59181771 (GRCh38)
Gene constraint: LOEUF 0.732 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.83
Residue 82: the wwe 2 domain

Full DTX4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DTX4 p.Ala342= Benign ★★ same type
DTX4 p.Thr284= Benign ★★ same type
DTX4 p.Val257Gly Benign ★★ same type
DTX4 p.Val355= Benign ★★ same type
DTX4 p.Ala171Thr Uncertain significance ★ ⚠ same type
DTX4 p.Ala288Pro Uncertain significance ★ ⚠ same type
DTX4 p.Ala303Gly Uncertain significance ★ ⚠ same type
DTX4 p.Ala310Thr 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/dtx4-p-asp82his (accessed [today's date]).

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