Is DTX3L p.Ser397Pro (c.1189T>C) pathogenic?

DTX3L p.Ser397Pro (c.1189T>C) is classified Uncertain significance in DTX3L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely benign (0.0982); Ultra-rare (popmax 0.0183%, amr).

How common is DTX3L p.Ser397Pro (c.1189T>C) in the general population?

DTX3L p.Ser397Pro (c.1189T>C) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

What do computational predictors say about DTX3L p.Ser397Pro (c.1189T>C)?

AlphaMissense predicts likely benign (score 0.0982) — an in-silico prediction, not a clinical call.

DTX3L p.Ser397Pro

c.1189T>C · rs779212382 · VCV3086126

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0982 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0982	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -10.91	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.4	GERP -5.7
Regional constraint	o/e 0.93	unconstrained · MANE · 7,317 bp · p 0.03 · regional, not allelic
Overall
CADD	0.063	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 0.0183% Admixed American · 11/60,002 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00785%

Overall 0.000743% 12/1,614,058 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,455
European (non-Finnish)	8.47e-05%	1,180,040

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: DTX3L
Protein: p.Ser397Pro
Coding: c.1189T>C
MANE Select: NM_138287
dbSNP: rs779212382
Type: single nucleotide variant
Location: chr3:122569278 (GRCh38)
Gene constraint: LOEUF 0.686 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.35 · 2 PDB

Full DTX3L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DTX3L p.Gly459Val Benign ★★ same type
DTX3L p.Ala370Val Uncertain significance ★ ⚠ same type
DTX3L p.Ala383Thr Uncertain significance ★ ⚠ same type
DTX3L p.Arg216Thr Uncertain significance ★ ⚠ same type
DTX3L p.Arg291His Uncertain significance ★ ⚠ same type
DTX3L p.Arg477Gly Uncertain significance ★ ⚠ same type
DTX3L p.Arg671Lys Uncertain significance ★ ⚠ same type
DTX3L p.Arg693Cys 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/dtx3l-p-ser397pro (accessed [today's date]).

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