Is DTX2 p.Lys398Arg (c.1193A>G) pathogenic?

DTX2 p.Lys398Arg (c.1193A>G) is classified Likely benign in DTX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). AlphaMissense: likely benign (0.0574); Ultra-rare (popmax 0.0778%, eas).

How common is DTX2 p.Lys398Arg (c.1193A>G) in the general population?

DTX2 p.Lys398Arg (c.1193A>G) is ultra-rare (popmax 0.0778%, eas) (gnomAD).

What do computational predictors say about DTX2 p.Lys398Arg (c.1193A>G)?

AlphaMissense predicts likely benign (score 0.0574) — an in-silico prediction, not a clinical call.

DTX2 p.Lys398Arg

c.1193A>G · rs573134039 · VCV3086108

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0574 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0778%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0574	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -4.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.66	GERP -2.7, phastCons 0.35
Regional constraint	o/e 0.06	constrained · MANE · 10 kb · p 1.4e-18 · regional, not allelic
Overall
CADD	13.23	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 0.0778% East Asian · 29/37,270 alleles

Filtering AF 0.0556% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0482%

Overall 0.0104% 88/842,770 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0778%	1,285
African / African-American	0.0748%	1,338
Remaining individualsnot grpmax-eligible	0.0499%	2,006
South Asian	0.00953%	10,497
Admixed American	0.00236%	42,372

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: DTX2
Protein: p.Lys398Arg
Coding: c.1193A>G
MANE Select: NM_001102594
dbSNP: rs573134039
Type: single nucleotide variant
Location: chr7:76500483 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.01 · 4 PDB
Residue 398: an α-helix

Full DTX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DTX2 p.Ala422= Likely benign ★★ same type
DTX2 p.Gly515= Likely benign ★★ same type
DTX2 p.Pro484= Benign ★★ same type
DTX2 p.Ala146Asp Uncertain significance ★ ⚠ same type
DTX2 p.Ala17Thr Uncertain significance ★ ⚠ same type
DTX2 p.Ala187Ser Uncertain significance ★ ⚠ same type
DTX2 p.Ala195Ser Uncertain significance ★ ⚠ same type
DTX2 p.Ala255Gly 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/dtx2-p-lys398arg (accessed [today's date]).

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