Is DUSP16 p.Ile281Val (c.841A>G) pathogenic?

DUSP16 p.Ile281Val (c.841A>G) is classified Uncertain significance in DUSP16 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: likely pathogenic (0.736); Ultra-rare (popmax 0.0405%, eas).

How common is DUSP16 p.Ile281Val (c.841A>G) in the general population?

DUSP16 p.Ile281Val (c.841A>G) is ultra-rare (popmax 0.0405%, eas) (gnomAD).

What do computational predictors say about DUSP16 p.Ile281Val (c.841A>G)?

AlphaMissense predicts likely pathogenic (score 0.736) — an in-silico prediction, not a clinical call.

DUSP16 p.Ile281Val

c.841A>G · VCV4015385

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.736 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0405%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.736	likely pathogenic
REVEL	0.658	pathogenic-leaning
SaProt	LLR -8.71	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 44 kb · p 0.0011 · regional, not allelic
Overall
CADD	25.6	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 0.0405% East Asian · 18/44,476 alleles

Filtering AF 0.0261% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0215%

Overall 0.00409% 65/1,587,936 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0405%	2,471
Remaining individualsnot grpmax-eligible	0.00817%	12,245
South Asian	0.00687%	14,560
Admixed American	0.00552%	18,119
Finnishnot grpmax-eligible	0.00314%	31,844
European (non-Finnish)	0.00257%	38,935
African / African-American	0.00136%	73,372

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: DUSP16
Protein: p.Ile281Val
Coding: c.841A>G
MANE Select: NM_030640
Type: single nucleotide variant
Location: chr12:12477990 (GRCh38)
Gene constraint: LOEUF 0.502 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 60.81 · 3 PDB
Residue 281: the tyrosine-protein phosphatase domain

Full DUSP16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP16 p.Ala2Thr Uncertain significance ★ ⚠ same type
DUSP16 p.Ala358Thr Uncertain significance ★ ⚠ same type
DUSP16 p.Ala73Val Uncertain significance ★ ⚠ same type
DUSP16 p.Arg130His Uncertain significance ★ ⚠ same type
DUSP16 p.Arg14Lys Uncertain significance ★ ⚠ same type
DUSP16 p.Arg208His Uncertain significance ★ ⚠ same type
DUSP16 p.Arg483Gln Uncertain significance ★ ⚠ same type
DUSP16 p.Arg598Cys 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/dusp16-p-ile281val (accessed [today's date]).

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