Is DUSP12 p.Val80Ala (c.239T>C) pathogenic?

DUSP12 p.Val80Ala (c.239T>C) is classified Uncertain significance in DUSP12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely pathogenic (0.6478); Absent from gnomAD v4.1.

How common is DUSP12 p.Val80Ala (c.239T>C) in the general population?

DUSP12 p.Val80Ala (c.239T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP12 p.Val80Ala (c.239T>C)?

AlphaMissense predicts likely pathogenic (score 0.6478) — an in-silico prediction, not a clinical call.

DUSP12 p.Val80Ala

c.239T>C · VCV4662514

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6478 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6478	likely pathogenic
REVEL	0.62	indeterminate
SaProt	LLR -11.17	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 3.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,142 bp · p 0.25 · 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

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: DUSP12
Protein: p.Val80Ala
Coding: c.239T>C
MANE Select: NM_007240
Type: single nucleotide variant
Location: chr1:161750040 (GRCh38)
Gene constraint: LOEUF 0.945 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.21 · 2 PDB
Residue 80: the tyrosine-protein phosphatase domain; a β-strand

Full DUSP12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP12 p.Ala167Val Uncertain significance ★ ⚠ same type
DUSP12 p.Arg20Ser Uncertain significance ★ ⚠ same type
DUSP12 p.Arg222Ser Uncertain significance ★ ⚠ same type
DUSP12 p.Arg238Cys Uncertain significance ★ ⚠ same type
DUSP12 p.Arg77His Uncertain significance ★ ⚠ same type
DUSP12 p.Asp9Asn Uncertain significance ★ ⚠ same type
DUSP12 p.Gln306Arg Uncertain significance ★ ⚠ same type
DUSP12 p.Glu107Val 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/dusp12-p-val80ala (accessed [today's date]).

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