Is DUSP6 p.Ala57Asp (c.170C>A) pathogenic?

DUSP6 p.Ala57Asp (c.170C>A) is classified Uncertain significance in DUSP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely pathogenic (0.8354); Absent from gnomAD v4.1.

How common is DUSP6 p.Ala57Asp (c.170C>A) in the general population?

DUSP6 p.Ala57Asp (c.170C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP6 p.Ala57Asp (c.170C>A)?

AlphaMissense predicts likely pathogenic (score 0.8354) — an in-silico prediction, not a clinical call.

DUSP6 p.Ala57Asp

c.170C>A · VCV4662597

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8354 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8354	likely pathogenic
REVEL	0.379	indeterminate
SaProt	LLR -8.79	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 1,392 bp · p 0.98 · regional, not allelic
Overall
CADD	29.0	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

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.Ala57Asp
Coding: c.170C>A
MANE Select: NM_001946
Type: single nucleotide variant
Location: chr12:89351870 (GRCh38)
Gene constraint: LOEUF 0.45 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 76.13 · 2 PDB
Residue 57: the rhodanese domain

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

Similar variants

DUSP6 p.Ala57Thr Uncertain significance ★★ ⚠ same residue
DUSP6 p.Ala141Asp 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
DUSP6 c.401-113T>A 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-ala57asp (accessed [today's date]).

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