Is DUSP26 p.His151Arg (c.452A>G) pathogenic?

DUSP26 p.His151Arg (c.452A>G) is classified Uncertain significance in DUSP26 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-02). AlphaMissense: likely pathogenic (0.9949); Very rare (popmax 0.00161%, nfe).

How common is DUSP26 p.His151Arg (c.452A>G) in the general population?

DUSP26 p.His151Arg (c.452A>G) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about DUSP26 p.His151Arg (c.452A>G)?

AlphaMissense predicts likely pathogenic (score 0.9949) — an in-silico prediction, not a clinical call.

DUSP26 p.His151Arg

c.452A>G · VCV4662562

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9949 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9949	likely pathogenic · top 8% in DUSP26
REVEL	0.98	strongly pathogenic-leaning
SaProt	LLR -14.15	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.1, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 5,499 bp · p 0.00019 · regional, not allelic
Overall
CADD	27.7	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

Grpmax group 0.00161% European (non-Finnish) · 19/1,178,360 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000831%

Overall 0.00118% 19/1,609,906 alleles · very rare exomes 14/1,458,022 · genomes 5/151,884 · joint denominator

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: DUSP26
Protein: p.His151Arg
Coding: c.452A>G
MANE Select: NM_024025
Type: single nucleotide variant
Location: chr8:33592197 (GRCh38)
Gene constraint: LOEUF 0.977 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.35 · 4 PDB
Residue 151: the tyrosine-protein phosphatase domain; a β-strand

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-his151arg (accessed [today's date]).

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