Is DTX1 p.Val363Met (c.1087G>A) pathogenic?

DTX1 p.Val363Met (c.1087G>A) is classified Uncertain significance in DTX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely pathogenic (0.6842); Very rare (popmax 8.48e-05%, nfe).

How common is DTX1 p.Val363Met (c.1087G>A) in the general population?

DTX1 p.Val363Met (c.1087G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DTX1 p.Val363Met (c.1087G>A)?

AlphaMissense predicts likely pathogenic (score 0.6842) — an in-silico prediction, not a clinical call.

DTX1 p.Val363Met

c.1087G>A · VCV4245280

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6842 · ACMG-weighted

gnomAD v4.1

Rare

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

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6842	likely pathogenic
REVEL	0.071	moderately benign-leaning
SaProt	LLR -9.38	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.2	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 17 kb · p 0.49 · regional, not allelic
Overall
CADD	28.7	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) · 1/1,179,804 alleles

Overall 6.84e-05% 1/1,461,072 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: DTX1
Protein: p.Val363Met
Coding: c.1087G>A
MANE Select: NM_004416
Type: single nucleotide variant
Location: chr12:113093622 (GRCh38)
Gene constraint: LOEUF 0.74 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.10 · 5 PDB
Residue 363: the 'disordered' region

Full DTX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DTX1 p.Gly445Asp Uncertain significance ★★ ⚠ same type
DTX1 p.Ser101= Benign ★★ same type
DTX1 p.Ala226Glu Uncertain significance ★ ⚠ same type
DTX1 p.Ala226Thr Uncertain significance ★ ⚠ same type
DTX1 p.Ala256Ser Uncertain significance ★ ⚠ same type
DTX1 p.Ala260Val Uncertain significance ★ ⚠ same type
DTX1 p.Ala267Pro Uncertain significance ★ ⚠ same type
DTX1 p.Ala275Val 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/dtx1-p-val363met (accessed [today's date]).

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