Is DTX3 p.Pro329Ser (c.985C>T) pathogenic?

DTX3 p.Pro329Ser (c.985C>T) is classified Uncertain significance in DTX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-27). AlphaMissense: ambiguous (0.5114); Absent from gnomAD v4.1.

How common is DTX3 p.Pro329Ser (c.985C>T) in the general population?

DTX3 p.Pro329Ser (c.985C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DTX3 p.Pro329Ser (c.985C>T)?

AlphaMissense predicts ambiguous (score 0.5114) — an in-silico prediction, not a clinical call.

DTX3 p.Pro329Ser

c.985C>T · rs2540579907 · VCV2339241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5114 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5114	ambiguous
REVEL	0.163	moderately benign-leaning
SaProt	LLR -5.91	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.67, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 1,819 bp · p 1.3e-18 · regional, not allelic
Overall
CADD	24.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DTX3
Protein: p.Pro329Ser
Coding: c.985C>T
MANE Select: NM_178502
dbSNP: rs2540579907
Type: single nucleotide variant
Location: chr12:57609093 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI 0.78 (gnomAD)
Structure: AlphaFold pLDDT 83.28

Full DTX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DTX3 p.Ala120Thr Uncertain significance ★ ⚠ same type
DTX3 p.Ala198Ser Uncertain significance ★ ⚠ same type
DTX3 p.Ala70Thr Uncertain significance ★ ⚠ same type
DTX3 p.Arg119His Uncertain significance ★ ⚠ same type
DTX3 p.Arg136Pro Uncertain significance ★ ⚠ same type
DTX3 p.Arg136Trp Uncertain significance ★ ⚠ same type
DTX3 p.Arg152Cys Uncertain significance ★ ⚠ same type
DTX3 p.Arg154Leu 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/dtx3-p-pro329ser (accessed [today's date]).

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