Is DTX2 p.Gly515Asp (c.1544G>A) pathogenic?

DTX2 p.Gly515Asp (c.1544G>A) is classified Uncertain significance in DTX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-07). AlphaMissense: likely pathogenic (0.9308); Absent from gnomAD v4.1.

How common is DTX2 p.Gly515Asp (c.1544G>A) in the general population?

DTX2 p.Gly515Asp (c.1544G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DTX2 p.Gly515Asp (c.1544G>A)?

AlphaMissense predicts likely pathogenic (score 0.9308) — an in-silico prediction, not a clinical call.

DTX2 p.Gly515Asp

c.1544G>A · rs1277120224 · VCV2323428

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9308 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,610,800)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9308	likely pathogenic
REVEL	0.73	pathogenic-leaning
SaProt	LLR -11.64	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,279 bp · p 0.18 · regional, not allelic
Overall
CADD	24.9	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

No allele count reported in gnomAD v4.1 (AN 1,610,800). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DTX2
Protein: p.Gly515Asp
Coding: c.1544G>A
MANE Select: NM_001102594
dbSNP: rs1277120224
Type: single nucleotide variant
Location: chr7:76503580 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.01 · 4 PDB

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

Similar variants

DTX2 p.Gly515= Likely benign ★★ same residue
DTX2 p.Ala422= 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-gly515asp (accessed [today's date]).

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