Is DTX3 p.Pro151Ser (c.451C>T) pathogenic?

DTX3 p.Pro151Ser (c.451C>T) is classified Uncertain significance in DTX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-27). AlphaMissense: likely benign (0.0767); Ultra-rare (popmax 0.0578%, sas).

How common is DTX3 p.Pro151Ser (c.451C>T) in the general population?

DTX3 p.Pro151Ser (c.451C>T) is ultra-rare (popmax 0.0578%, sas) (gnomAD).

What do computational predictors say about DTX3 p.Pro151Ser (c.451C>T)?

AlphaMissense predicts likely benign (score 0.0767) — an in-silico prediction, not a clinical call.

DTX3 p.Pro151Ser

c.451C>T · VCV4662387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0767 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0578%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0767	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -9.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Regional constraint	o/e 0.98	unconstrained · MANE · 811 bp · p 0.82 · regional, not allelic
Overall
CADD	21.2	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

Grpmax group 0.0578% South Asian · 51/88,186 alleles

Filtering AF 0.0452% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0406%

Overall 0.00392% 56/1,428,122 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0578%	1,729
European (non-Finnish)	0.000431%	231,808

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: DTX3
Protein: p.Pro151Ser
Coding: c.451C>T
MANE Select: NM_178502
Type: single nucleotide variant
Location: chr12:57607314 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI 0.78 (gnomAD)
Structure: AlphaFold pLDDT 83.28
Residue 151: the 'disordered' region

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-pro151ser (accessed [today's date]).

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