Is DTX2 p.Leu65Val (c.193T>G) pathogenic?

DTX2 p.Leu65Val (c.193T>G) is classified Uncertain significance in DTX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-13). AlphaMissense: likely pathogenic (0.5686); Absent from gnomAD v4.1.

How common is DTX2 p.Leu65Val (c.193T>G) in the general population?

DTX2 p.Leu65Val (c.193T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DTX2 p.Leu65Val (c.193T>G)?

AlphaMissense predicts likely pathogenic (score 0.5686) — an in-silico prediction, not a clinical call.

DTX2 p.Leu65Val

c.193T>G · rs2116364336 · VCV2536875

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5686 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5686	likely pathogenic
REVEL	0.49	indeterminate
SaProt	LLR -10.41	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.9	GERP -1.8, phastCons 0.89
Regional constraint	o/e 0.76	unconstrained · MANE · 2,592 bp · p 1.6e-06 · regional, not allelic
Overall
CADD	19.68	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: DTX2
Protein: p.Leu65Val
Coding: c.193T>G
MANE Select: NM_001102594
dbSNP: rs2116364336
Type: single nucleotide variant
Location: chr7:76480702 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.01 · 4 PDB
Residue 65: the wwe 1 domain

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-leu65val (accessed [today's date]).

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