Is DUSP26 p.Glu47Lys (c.139G>A) pathogenic?

DUSP26 p.Glu47Lys (c.139G>A) is classified Uncertain significance in DUSP26 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely pathogenic (0.9509); Very rare (popmax 0.00333%, amr).

How common is DUSP26 p.Glu47Lys (c.139G>A) in the general population?

DUSP26 p.Glu47Lys (c.139G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about DUSP26 p.Glu47Lys (c.139G>A)?

AlphaMissense predicts likely pathogenic (score 0.9509) — an in-silico prediction, not a clinical call.

DUSP26 p.Glu47Lys

c.139G>A · VCV4245553

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9509 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9509	likely pathogenic
REVEL	0.296	indeterminate
SaProt	LLR -9.12	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.73 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 5,499 bp · p 0.00019 · regional, not allelic
Overall
CADD	25.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,992 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00198% 32/1,614,076 alleles · very rare exomes 31/1,461,850 · genomes 1/152,226 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,996
European (non-Finnish)	0.00229%	43,705
East Asian	0.00223%	44,872
South Asian	0.0022%	45,533

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.Glu47Lys
Coding: c.139G>A
MANE Select: NM_024025
Type: single nucleotide variant
Location: chr8:33597377 (GRCh38)
Gene constraint: LOEUF 0.977 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.35 · 4 PDB
Residue 47: 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-glu47lys (accessed [today's date]).

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