Is DTX4 p.Val34Ile (c.100G>A) pathogenic?

DTX4 p.Val34Ile (c.100G>A) is classified Uncertain significance in DTX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely benign (0.1148); No allele count reported in gnomAD v4.1 (AN 1,601,074).

How common is DTX4 p.Val34Ile (c.100G>A) in the general population?

DTX4 p.Val34Ile (c.100G>A) is no allele count reported in gnomAD v4.1 (AN 1,601,074) (gnomAD).

What do computational predictors say about DTX4 p.Val34Ile (c.100G>A)?

AlphaMissense predicts likely benign (score 0.1148) — an in-silico prediction, not a clinical call.

DTX4 p.Val34Ile

c.100G>A · rs2496374087 · VCV3086135

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1148 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,601,074)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1148	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -8.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP -3.4, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 32 kb · p 2.6e-05 · regional, not allelic
Overall
CADD	22.0	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

No allele count reported in gnomAD v4.1 (AN 1,601,074). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DTX4
Protein: p.Val34Ile
Coding: c.100G>A
MANE Select: NM_015177
dbSNP: rs2496374087
Type: single nucleotide variant
Location: chr11:59172695 (GRCh38)
Gene constraint: LOEUF 0.732 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.83
Residue 34: the wwe 1 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-val34ile (accessed [today's date]).

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