Is DUSP5 p.Ser61Trp (c.182C>G) pathogenic?

DUSP5 p.Ser61Trp (c.182C>G) is classified Uncertain significance in DUSP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-15). AlphaMissense: ambiguous (0.5202); Very rare (popmax 0.00146%, sas).

How common is DUSP5 p.Ser61Trp (c.182C>G) in the general population?

DUSP5 p.Ser61Trp (c.182C>G) is very rare (popmax 0.00146%, sas) (gnomAD).

What do computational predictors say about DUSP5 p.Ser61Trp (c.182C>G)?

AlphaMissense predicts ambiguous (score 0.5202) — an in-silico prediction, not a clinical call.

DUSP5 p.Ser61Trp

c.182C>G · rs1357915575 · VCV2261662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5202 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00146%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5202	ambiguous
REVEL	0.213	benign-leaning
SaProt	LLR -9.98	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP -3.7, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 8,933 bp · p 6.1e-05 · regional, not allelic
Overall
CADD	25.3	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

Grpmax group 0.00146% South Asian · 1/68,342 alleles

Overall 0.000139% 2/1,434,752 alleles · very rare exomes 2/1,285,626 · genomes 0/149,126 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00146%	68,342
European (non-Finnish)	9.18e-05%	1,089,852

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.Ser61Trp
Coding: c.182C>G
MANE Select: NM_004419
dbSNP: rs1357915575
Type: single nucleotide variant
Location: chr10:110498303 (GRCh38)
Gene constraint: LOEUF 1.069 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.76 · 1 PDB
Residue 61: 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-ser61trp (accessed [today's date]).

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