Is DUSP26 p.Leu141Arg (c.422T>G) pathogenic?

DUSP26 p.Leu141Arg (c.422T>G) is classified Uncertain significance in DUSP26 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-09). AlphaMissense: likely pathogenic (0.6262); Absent from gnomAD v4.1.

How common is DUSP26 p.Leu141Arg (c.422T>G) in the general population?

DUSP26 p.Leu141Arg (c.422T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP26 p.Leu141Arg (c.422T>G)?

AlphaMissense predicts likely pathogenic (score 0.6262) — an in-silico prediction, not a clinical call.

DUSP26 p.Leu141Arg

c.422T>G · rs2487488137 · VCV2287965

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6262 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6262	likely pathogenic
REVEL	0.629	indeterminate
SaProt	LLR -11.77	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 5,499 bp · p 0.00019 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DUSP26
Protein: p.Leu141Arg
Coding: c.422T>G
MANE Select: NM_024025
dbSNP: rs2487488137
Type: single nucleotide variant
Location: chr8:33593547 (GRCh38)
Gene constraint: LOEUF 0.977 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.35 · 4 PDB
Residue 141: the tyrosine-protein phosphatase domain; an α-helix

Full DUSP26 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP26 p.Ala9Ser Uncertain significance ★ ⚠ same type
DUSP26 p.Arg100Gln Uncertain significance ★ ⚠ same type
DUSP26 p.Arg139Trp Uncertain significance ★ ⚠ same type
DUSP26 p.Arg16Cys Uncertain significance ★ ⚠ same type
DUSP26 p.Arg16His Uncertain significance ★ ⚠ same type
DUSP26 p.Arg19Gln Uncertain significance ★ ⚠ same type
DUSP26 p.Arg19Trp Uncertain significance ★ ⚠ same type
DUSP26 p.Arg81Trp 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/dusp26-p-leu141arg (accessed [today's date]).

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