Is DUSP5 p.Arg63Ser (c.187C>A) pathogenic?

DUSP5 p.Arg63Ser (c.187C>A) is classified Uncertain significance in DUSP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely benign (0.2264); Very rare (popmax 0.00151%, sas).

How common is DUSP5 p.Arg63Ser (c.187C>A) in the general population?

DUSP5 p.Arg63Ser (c.187C>A) is very rare (popmax 0.00151%, sas) (gnomAD).

What do computational predictors say about DUSP5 p.Arg63Ser (c.187C>A)?

AlphaMissense predicts likely benign (score 0.2264) — an in-silico prediction, not a clinical call.

DUSP5 p.Arg63Ser

c.187C>A · VCV4662592

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2264 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00151%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2264	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -9.05	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 1.9, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 8,933 bp · p 6.1e-05 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00151% South Asian · 1/66,400 alleles

Overall 7e-05% 1/1,428,248 alleles · very rare exomes 1/1,279,126 · genomes 0/149,122 · joint denominator

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: DUSP5
Protein: p.Arg63Ser
Coding: c.187C>A
MANE Select: NM_004419
Type: single nucleotide variant
Location: chr10:110498308 (GRCh38)
Gene constraint: LOEUF 1.069 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.76 · 1 PDB
Residue 63: the rhodanese domain

Full DUSP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP5 p.Asp291Asn Uncertain significance ★★ ⚠ same type
DUSP5 p.Ala55Ser Benign ★★ same type
DUSP5 p.Ala104Val Uncertain significance ★ ⚠ same type
DUSP5 p.Ala59Pro Uncertain significance ★ ⚠ same type
DUSP5 p.Arg121Leu Uncertain significance ★ ⚠ same type
DUSP5 p.Arg16Ser Uncertain significance ★ ⚠ same type
DUSP5 p.Arg213Gln Uncertain significance ★ ⚠ same type
DUSP5 p.Arg269Cys 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/dusp5-p-arg63ser (accessed [today's date]).

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