Is DUSP8 p.Cys51Ser (c.152G>C) pathogenic?

DUSP8 p.Cys51Ser (c.152G>C) is classified Uncertain significance in DUSP8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-09). AlphaMissense: likely pathogenic (0.6533); Absent from gnomAD v4.1.

How common is DUSP8 p.Cys51Ser (c.152G>C) in the general population?

DUSP8 p.Cys51Ser (c.152G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP8 p.Cys51Ser (c.152G>C)?

AlphaMissense predicts likely pathogenic (score 0.6533) — an in-silico prediction, not a clinical call.

DUSP8 p.Cys51Ser

c.152G>C · VCV3505938

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6533 · 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	0.6533	likely pathogenic
REVEL	0.396	indeterminate
SaProt	LLR -7.42	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 5.7	phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 8,318 bp · p 5.2e-15 · regional, not allelic
Overall
CADD	28.8	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: DUSP8
Protein: p.Cys51Ser
Coding: c.152G>C
MANE Select: NM_004420
Type: single nucleotide variant
Location: chr11:1565675 (GRCh38)
Gene constraint: LOEUF 0.813 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 63.99 · 1 PDB
Residue 51: the rhodanese domain

Full DUSP8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP8 p.Asp271= Benign ★★ same type
DUSP8 p.Ala101Thr Uncertain significance ★ ⚠ same type
DUSP8 p.Ala272Ser Uncertain significance ★ ⚠ same type
DUSP8 p.Ala305Thr Uncertain significance ★ ⚠ same type
DUSP8 p.Ala325Pro Uncertain significance ★ ⚠ same type
DUSP8 p.Ala345Val Uncertain significance ★ ⚠ same type
DUSP8 p.Ala366Val Uncertain significance ★ ⚠ same type
DUSP8 p.Ala403Val 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/dusp8-p-cys51ser (accessed [today's date]).

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