Is DUSP19 p.Leu96Val (c.286C>G) pathogenic?

DUSP19 p.Leu96Val (c.286C>G) is classified Uncertain significance in DUSP19 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.2033); Ultra-rare (popmax 0.0565%, sas).

How common is DUSP19 p.Leu96Val (c.286C>G) in the general population?

DUSP19 p.Leu96Val (c.286C>G) is ultra-rare (popmax 0.0565%, sas) (gnomAD).

What do computational predictors say about DUSP19 p.Leu96Val (c.286C>G)?

AlphaMissense predicts likely benign (score 0.2033) — an in-silico prediction, not a clinical call.

DUSP19 p.Leu96Val

c.286C>G · rs749111793 · VCV2566118

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2033 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0565%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2033	likely benign
REVEL	0.278	benign-leaning
SaProt	LLR -8.82	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 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 17 kb · p 0.9 · regional, not allelic
Overall
CADD	25.7	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 0.0565% South Asian · 51/90,240 alleles

Filtering AF 0.0441% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0397%

Overall 0.00385% 62/1,610,334 alleles · ultra-rare exomes 59/1,458,240 · genomes 3/152,094 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0565%	1,769
Middle Eastern	0.0329%	3,039
Remaining individualsnot grpmax-eligible	0.00481%	20,795
European (non-Finnish)	0.000509%	196,568

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: DUSP19
Protein: p.Leu96Val
Coding: c.286C>G
MANE Select: NM_080876
dbSNP: rs749111793
Type: single nucleotide variant
Location: chr2:183087052 (GRCh38)
Gene constraint: LOEUF 1.516 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.39 · 4 PDB
Residue 96: the tyrosine-protein phosphatase domain; a β-strand

Full DUSP19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP19 p.Ala10Val Uncertain significance ★ ⚠ same type
DUSP19 p.Arg141Gly Uncertain significance ★ ⚠ same type
DUSP19 p.Arg198Cys Uncertain significance ★ ⚠ same type
DUSP19 p.Arg198His Uncertain significance ★ ⚠ same type
DUSP19 p.Arg211Gly Uncertain significance ★ ⚠ same type
DUSP19 p.Asn167Ser Uncertain significance ★ ⚠ same type
DUSP19 p.Asp143Gly Uncertain significance ★ ⚠ same type
DUSP19 p.Asp37Gly 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/dusp19-p-leu96val (accessed [today's date]).

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