Is DTX2 p.Pro484= (c.1452C>G) pathogenic?

DTX2 p.Pro484= (c.1452C>G) is classified Benign in DTX2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-02-25). Common (popmax 6.16%, afr) — too common for a highly-penetrant pathogenic allele.

DTX2 p.Pro484=

Q: How common is DTX2 p.Pro484= (c.1452C>G) in the general population?

DTX2 p.Pro484= (c.1452C>G) is common (popmax 6.16%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1452C>G · rs73703182 · VCV776233

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.16%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.61	GERP -0.24, phastCons 0.001
Overall
CADD	8.332	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.16% African / African-American · 4,622/74,998 alleles

Filtering AF 6.01% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.95%

Overall 0.339% 5,460/1,612,968 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.16%	16
Remaining individualsnot grpmax-eligible	0.504%	198
Admixed American	0.488%	205
Middle Eastern	0.446%	224
South Asian	0.0307%	3,253
European (non-Finnish)	0.0147%	6,781
East Asian	0.00223%	44,878

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.Pro484=
Coding: c.1452C>G
MANE Select: NM_001102594
dbSNP: rs73703182
Type: single nucleotide variant
Location: chr7:76503488 (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.Ala422= Likely benign ★★ same type
DTX2 p.Gly515= Likely 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
DTX2 p.Ala258Val 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-pro484 (accessed [today's date]).

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