Is DUSP10 p.Val419Ile (c.1255G>A) pathogenic?

DUSP10 p.Val419Ile (c.1255G>A) is classified Uncertain significance in DUSP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). AlphaMissense: likely benign (0.2516); Ultra-rare (popmax 0.0357%, eas).

How common is DUSP10 p.Val419Ile (c.1255G>A) in the general population?

DUSP10 p.Val419Ile (c.1255G>A) is ultra-rare (popmax 0.0357%, eas) (gnomAD).

What do computational predictors say about DUSP10 p.Val419Ile (c.1255G>A)?

AlphaMissense predicts likely benign (score 0.2516) — an in-silico prediction, not a clinical call.

DUSP10 p.Val419Ile

c.1255G>A · rs116590328 · VCV3086244

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2516 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0357%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2516	likely benign
REVEL	0.244	benign-leaning
SaProt	LLR -8.98	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 7.7	GERP 1.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 37 kb · p 0.0053 · regional, not allelic
Overall
CADD	24.9	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 0.0357% East Asian · 16/44,870 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00235% 38/1,614,086 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0357%	2,804
South Asian	0.0121%	8,279
Remaining individualsnot grpmax-eligible	0.0032%	31,253
African / African-American	0.00267%	37,499
European (non-Finnish)	0.000593%	168,574

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.Val419Ile
Coding: c.1255G>A
MANE Select: NM_007207
dbSNP: rs116590328
Type: single nucleotide variant
Location: chr1:221702606 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 70.95 · 23 PDB
Residue 419: the tyrosine-protein phosphatase domain; an α-helix

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

Similar variants

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.Arg203Gln Uncertain significance ★ ⚠ same type
DUSP10 p.Arg203Trp Uncertain significance ★ ⚠ same type
DUSP10 p.Arg245Leu 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-val419ile (accessed [today's date]).

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