Is DUSP2 p.Ala265Pro (c.793G>C) pathogenic?

DUSP2 p.Ala265Pro (c.793G>C) is classified Uncertain significance in DUSP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-26). AlphaMissense: ambiguous (0.5536); Very rare (popmax 0.000169%, nfe).

How common is DUSP2 p.Ala265Pro (c.793G>C) in the general population?

DUSP2 p.Ala265Pro (c.793G>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about DUSP2 p.Ala265Pro (c.793G>C)?

AlphaMissense predicts ambiguous (score 0.5536) — an in-silico prediction, not a clinical call.

DUSP2 p.Ala265Pro

c.793G>C · VCV3505863

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5536 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5536	ambiguous
REVEL	0.429	indeterminate
SaProt	LLR -8.30	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,528 bp · p 0.41 · regional, not allelic
Overall
CADD	23.6	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 0.000169% European (non-Finnish) · 2/1,180,010 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,452 alleles · very rare

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: DUSP2
Protein: p.Ala265Pro
Coding: c.793G>C
MANE Select: NM_004418
Type: single nucleotide variant
Location: chr2:96143975 (GRCh38)
Gene constraint: LOEUF 1.442 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.59 · 1 PDB
Residue 265: an α-helix; the tyrosine-protein phosphatase domain

Full DUSP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP2 p.Ala265Val Uncertain significance ★ ⚠ same residue
DUSP2 p.Ala107Val Uncertain significance ★ ⚠ same type
DUSP2 p.Ala45Val Uncertain significance ★ ⚠ same type
DUSP2 p.Ala65Gly Uncertain significance ★ ⚠ same type
DUSP2 p.Arg263Cys Uncertain significance ★ ⚠ same type
DUSP2 p.Arg26His Uncertain significance ★ ⚠ same type
DUSP2 p.Arg26Ser Uncertain significance ★ ⚠ same type
DUSP2 p.Arg276Cys 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/dusp2-p-ala265pro (accessed [today's date]).

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