Is DUSP10 p.Arg203Gln (c.608G>A) pathogenic?

DUSP10 p.Arg203Gln (c.608G>A) is classified Uncertain significance in DUSP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-17). AlphaMissense: likely pathogenic (0.9842); Very rare (popmax 0.00445%, eas).

How common is DUSP10 p.Arg203Gln (c.608G>A) in the general population?

DUSP10 p.Arg203Gln (c.608G>A) is very rare (popmax 0.00445%, eas) (gnomAD).

What do computational predictors say about DUSP10 p.Arg203Gln (c.608G>A)?

AlphaMissense predicts likely pathogenic (score 0.9842) — an in-silico prediction, not a clinical call.

DUSP10 p.Arg203Gln

c.608G>A · rs1256262280 · VCV2486669

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9842 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9842	likely pathogenic
REVEL	0.403	indeterminate
SaProt	LLR -11.83	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 7.7	GERP 0.63, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 37 kb · p 0.0053 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 0.00445% East Asian · 2/44,902 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.00062% 10/1,614,070 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,451
Admixed American	0.00333%	30,005
Finnishnot grpmax-eligible	0.00156%	64,028
African / African-American	0.00134%	74,904
European (non-Finnish)	0.000339%	295,011

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: DUSP10
Protein: p.Arg203Gln
Coding: c.608G>A
MANE Select: NM_007207
dbSNP: rs1256262280
Type: single nucleotide variant
Location: chr1:221739137 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 70.95 · 23 PDB
Residue 203: the rhodanese domain; an α-helix; the 'interaction with map kinases' region

Full DUSP10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP10 p.Arg203Trp Uncertain significance ★ ⚠ same residue
DUSP10 p.Ala197Thr Uncertain significance ★ ⚠ same type
DUSP10 p.Ala300Thr Uncertain significance ★ ⚠ same type
DUSP10 p.Ala47Val Uncertain significance ★ ⚠ same type
DUSP10 p.Ala55Pro Uncertain significance ★ ⚠ same type
DUSP10 p.Ala99Ser Uncertain significance ★ ⚠ same type
DUSP10 p.Arg245Leu Uncertain significance ★ same type
DUSP10 p.Arg345Gln 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/dusp10-p-arg203gln (accessed [today's date]).

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