Is DTX4 p.Gln120Pro (c.359A>C) pathogenic?

DTX4 p.Gln120Pro (c.359A>C) is classified Uncertain significance in DTX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: ambiguous (0.341); Very rare (popmax 8.48e-05%, nfe).

How common is DTX4 p.Gln120Pro (c.359A>C) in the general population?

DTX4 p.Gln120Pro (c.359A>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DTX4 p.Gln120Pro (c.359A>C)?

AlphaMissense predicts ambiguous (score 0.341) — an in-silico prediction, not a clinical call.

DTX4 p.Gln120Pro

c.359A>C · VCV4245316

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.341 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.341	ambiguous
REVEL	0.444	indeterminate
SaProt	LLR -9.75	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 0.3, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 32 kb · p 2.6e-05 · regional, not allelic
Overall
CADD	26.3	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 8.48e-05% European (non-Finnish) · 1/1,179,892 alleles

Overall 6.84e-05% 1/1,461,708 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: DTX4
Protein: p.Gln120Pro
Coding: c.359A>C
MANE Select: NM_015177
Type: single nucleotide variant
Location: chr11:59181886 (GRCh38)
Gene constraint: LOEUF 0.732 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.83
Residue 120: 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-gln120pro (accessed [today's date]).

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