Is DUSP11 p.Ile196Val (c.586A>G) pathogenic?

DUSP11 p.Ile196Val (c.586A>G) is classified Uncertain significance in DUSP11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). AlphaMissense: likely benign (0.1145); Ultra-rare (popmax 0.0193%, nfe).

How common is DUSP11 p.Ile196Val (c.586A>G) in the general population?

DUSP11 p.Ile196Val (c.586A>G) is ultra-rare (popmax 0.0193%, nfe) (gnomAD).

What do computational predictors say about DUSP11 p.Ile196Val (c.586A>G)?

AlphaMissense predicts likely benign (score 0.1145) — an in-silico prediction, not a clinical call.

DUSP11 p.Ile196Val

c.586A>G · rs140704867 · VCV2374876

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1145 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0193%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1145	likely benign
REVEL	0.267	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -0.25, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 17 kb · p 0.86 · regional, not allelic
Overall
CADD	18.0	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 is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I243V vs ClinVar I196V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0193% European (non-Finnish) · 228/1,179,488 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0164%

Overall 0.0151% 244/1,613,372 alleles · ultra-rare exomes 234/1,461,146 · genomes 10/152,226 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0193%	5,173
Remaining individualsnot grpmax-eligible	0.0176%	5,678
African / African-American	0.004%	24,974
Admixed American	0.00333%	30,001

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.Ile196Val
Coding: c.586A>G
MANE Select: NM_003584
dbSNP: rs140704867
Type: single nucleotide variant
Location: chr2:73766859 (GRCh38)
Gene constraint: LOEUF 1.286 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.34 · 3 PDB

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-ile196val (accessed [today's date]).

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