Is DUSP2 p.Ala265Val (c.794C>T) pathogenic?

DUSP2 p.Ala265Val (c.794C>T) is classified Uncertain significance in DUSP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely pathogenic (0.7722); Very rare (popmax 8.47e-05%, nfe).

How common is DUSP2 p.Ala265Val (c.794C>T) in the general population?

DUSP2 p.Ala265Val (c.794C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DUSP2 p.Ala265Val (c.794C>T)?

AlphaMissense predicts likely pathogenic (score 0.7722) — an in-silico prediction, not a clinical call.

DUSP2 p.Ala265Val

c.794C>T · rs1205743329 · VCV2245016

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7722 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7722	likely pathogenic
REVEL	0.455	indeterminate
SaProt	LLR -7.58	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,528 bp · p 0.41 · regional, not allelic
Overall
CADD	26.7	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 8.47e-05% European (non-Finnish) · 1/1,180,012 alleles

Overall 0.000137% 2/1,461,468 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)grpmax	8.47e-05%	1,180,012

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala265Val
Coding: c.794C>T
MANE Select: NM_004418
dbSNP: rs1205743329
Type: single nucleotide variant
Location: chr2:96143974 (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.Ala265Pro 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-ala265val (accessed [today's date]).

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