Is DTX3 p.Ala198Ser (c.592G>T) pathogenic?

DTX3 p.Ala198Ser (c.592G>T) is classified Uncertain significance in DTX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: ambiguous (0.4992); Rare (popmax 0.151%, afr).

How common is DTX3 p.Ala198Ser (c.592G>T) in the general population?

DTX3 p.Ala198Ser (c.592G>T) is rare (popmax 0.151%, afr) (gnomAD).

What do computational predictors say about DTX3 p.Ala198Ser (c.592G>T)?

AlphaMissense predicts ambiguous (score 0.4992) — an in-silico prediction, not a clinical call.

DTX3 p.Ala198Ser

c.592G>T · rs201715772 · VCV3086123

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4992 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.151%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4992	ambiguous
REVEL	0.105	moderately benign-leaning
SaProt	LLR -7.05	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 1,819 bp · p 1.3e-18 · regional, not allelic
Overall
CADD	24.1	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 0.151% African / African-American · 113/75,052 alleles

Filtering AF 0.128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.12%

Overall 0.00904% 146/1,614,158 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.151%	664
Middle Eastern	0.0165%	6,060
Remaining individualsnot grpmax-eligible	0.008%	12,501
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802
Admixed American	0.00666%	15,006
European (non-Finnish)	0.00178%	56,191

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.Ala198Ser
Coding: c.592G>T
MANE Select: NM_178502
dbSNP: rs201715772
Type: single nucleotide variant
Location: chr12:57607455 (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.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
DTX3 p.Arg41Gln 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-ala198ser (accessed [today's date]).

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