Is DUSP12 p.Leu289Ile (c.865C>A) pathogenic?

DUSP12 p.Leu289Ile (c.865C>A) is classified Uncertain significance in DUSP12 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.1377); Ultra-rare (popmax 0.0178%, eas).

How common is DUSP12 p.Leu289Ile (c.865C>A) in the general population?

DUSP12 p.Leu289Ile (c.865C>A) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about DUSP12 p.Leu289Ile (c.865C>A)?

AlphaMissense predicts likely benign (score 0.1377) — an in-silico prediction, not a clinical call.

DUSP12 p.Leu289Ile

c.865C>A · rs558041696 · VCV2455824

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1377 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1377	likely benign
REVEL	0.13	moderately benign-leaning
SaProt	LLR -6.51	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 5.8	GERP 3.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,142 bp · p 0.25 · regional, not allelic
Overall
CADD	24.8	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 0.0178% East Asian · 8/44,832 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000683% 11/1,610,256 alleles · ultra-rare exomes 8/1,457,972 · genomes 3/152,284 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,604
Remaining individualsnot grpmax-eligible	0.00321%	31,172
South Asian	0.0011%	90,522

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: DUSP12
Protein: p.Leu289Ile
Coding: c.865C>A
MANE Select: NM_007240
dbSNP: rs558041696
Type: single nucleotide variant
Location: chr1:161756789 (GRCh38)
Gene constraint: LOEUF 0.945 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.21 · 2 PDB

Full DUSP12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP12 p.Leu289Phe Uncertain significance ★ ⚠ same residue
DUSP12 p.Ala167Val Uncertain significance ★ ⚠ same type
DUSP12 p.Arg20Ser Uncertain significance ★ ⚠ same type
DUSP12 p.Arg222Ser Uncertain significance ★ ⚠ same type
DUSP12 p.Arg238Cys Uncertain significance ★ ⚠ same type
DUSP12 p.Arg77His Uncertain significance ★ ⚠ same type
DUSP12 p.Asp9Asn Uncertain significance ★ ⚠ same type
DUSP12 p.Gln306Arg 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/dusp12-p-leu289ile (accessed [today's date]).

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