Is DUSP26 p.Arg19Trp (c.55C>T) pathogenic?

DUSP26 p.Arg19Trp (c.55C>T) is classified Uncertain significance in DUSP26 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-29). AlphaMissense: ambiguous (0.371); Ultra-rare (popmax 0.02%, amr).

How common is DUSP26 p.Arg19Trp (c.55C>T) in the general population?

DUSP26 p.Arg19Trp (c.55C>T) is ultra-rare (popmax 0.02%, amr) (gnomAD).

What do computational predictors say about DUSP26 p.Arg19Trp (c.55C>T)?

AlphaMissense predicts ambiguous (score 0.371) — an in-silico prediction, not a clinical call.

DUSP26 p.Arg19Trp

c.55C>T · rs114901124 · VCV3086304

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.371 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.371	ambiguous
REVEL	0.207	benign-leaning
SaProt	LLR -7.86	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.49 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.5	GERP -0.34, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 5,499 bp · p 0.00019 · regional, not allelic
Overall
CADD	26.9	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 0.02% Admixed American · 12/60,000 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00508% 82/1,614,054 alleles · ultra-rare exomes 71/1,461,810 · genomes 11/152,244 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	5,000
European (non-Finnish)	0.00559%	17,879
Remaining individualsnot grpmax-eligible	0.0032%	31,251
African / African-American	0.00133%	75,038
South Asian	0.0011%	91,068

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.Arg19Trp
Coding: c.55C>T
MANE Select: NM_024025
dbSNP: rs114901124
Type: single nucleotide variant
Location: chr8:33597461 (GRCh38)
Gene constraint: LOEUF 0.977 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.35 · 4 PDB

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

Similar variants

DUSP26 p.Arg19Gln Uncertain significance ★ ⚠ same residue
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.Arg81Trp Uncertain significance ★ ⚠ same type
DUSP26 p.Arg85Cys 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-arg19trp (accessed [today's date]).

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