Is DUSP6 p.Gln270His (c.810G>T) pathogenic?

DUSP6 p.Gln270His (c.810G>T) is classified Uncertain significance in DUSP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-06). AlphaMissense: likely pathogenic (0.8016); Absent from gnomAD v4.1.

How common is DUSP6 p.Gln270His (c.810G>T) in the general population?

DUSP6 p.Gln270His (c.810G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP6 p.Gln270His (c.810G>T)?

AlphaMissense predicts likely pathogenic (score 0.8016) — an in-silico prediction, not a clinical call.

DUSP6 p.Gln270His

c.810G>T · VCV4741431

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8016 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8016	likely pathogenic
REVEL	0.613	indeterminate
SaProt	LLR -11.79	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 1,389 bp · p 0.00012 · regional, not allelic
Overall
CADD	25.2	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: DUSP6
Protein: p.Gln270His
Coding: c.810G>T
MANE Select: NM_001946
Type: single nucleotide variant
Location: chr12:89350616 (GRCh38)
Gene constraint: LOEUF 0.45 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 76.13 · 2 PDB
Residue 270: the tyrosine-protein phosphatase domain; an α-helix

Full DUSP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP6 p.Gln270Arg Uncertain significance ★ ⚠ same residue
DUSP6 p.Ala141Asp Uncertain significance ★★ ⚠ same type
DUSP6 p.Ala57Thr Uncertain significance ★★ ⚠ same type
DUSP6 p.Asp93Glu Uncertain significance ★★ ⚠ same type
DUSP6 p.Glu32Lys Uncertain significance ★★ ⚠ same type
DUSP6 p.Gly30Cys Uncertain significance ★★ ⚠ same type
DUSP6 p.Phe77Ile Uncertain significance ★★ ⚠ same type
DUSP6 c.400+231T>C Benign ★★ 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/dusp6-p-gln270his (accessed [today's date]).

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