Is DUSP11 p.Ile179Val (c.535A>G) pathogenic?

DUSP11 p.Ile179Val (c.535A>G) is classified Uncertain significance in DUSP11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). AlphaMissense: likely benign (0.1012); Very rare (popmax 0.00229%, nfe).

How common is DUSP11 p.Ile179Val (c.535A>G) in the general population?

DUSP11 p.Ile179Val (c.535A>G) is very rare (popmax 0.00229%, nfe) (gnomAD).

What do computational predictors say about DUSP11 p.Ile179Val (c.535A>G)?

AlphaMissense predicts likely benign (score 0.1012) — an in-silico prediction, not a clinical call.

DUSP11 p.Ile179Val

c.535A>G · VCV4015375

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1012 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Computational evidence

Protein change
AlphaMissense	0.1012	likely benign
REVEL	0.543	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 17 kb · p 0.86 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I226V vs ClinVar I179V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00229% European (non-Finnish) · 27/1,178,520 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00174% 28/1,611,980 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00229%	43,649
Remaining individualsnot grpmax-eligible	0.0016%	62,398

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: DUSP11
Protein: p.Ile179Val
Coding: c.535A>G
MANE Select: NM_003584
Type: single nucleotide variant
Location: chr2:73767167 (GRCh38)
Gene constraint: LOEUF 1.286 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.34 · 3 PDB
Residue 179: the tyrosine-protein phosphatase domain; an α-helix

Full DUSP11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP11 c.178-7G>C Benign ★★ same type
DUSP11 c.794+5C>G Benign ★★ same type
DUSP11 c.-118G>A Benign ★★ same type
DUSP11 c.-104G>T Uncertain significance ★ ⚠ same type
DUSP11 c.-108G>T Uncertain significance ★ ⚠ same type
DUSP11 c.-116G>A Uncertain significance ★ ⚠ same type
DUSP11 c.-117C>G Uncertain significance ★ ⚠ same type
DUSP11 c.-117C>T 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/dusp11-p-ile179val (accessed [today's date]).

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