Is DUSP26 p.Arg16Cys (c.46C>T) pathogenic?

DUSP26 p.Arg16Cys (c.46C>T) is classified Uncertain significance in DUSP26 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: ambiguous (0.4664); Very rare (popmax 0.00667%, amr).

How common is DUSP26 p.Arg16Cys (c.46C>T) in the general population?

DUSP26 p.Arg16Cys (c.46C>T) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about DUSP26 p.Arg16Cys (c.46C>T)?

AlphaMissense predicts ambiguous (score 0.4664) — an in-silico prediction, not a clinical call.

DUSP26 p.Arg16Cys

c.46C>T · VCV4015419

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4664 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4664	ambiguous
REVEL	0.238	benign-leaning
SaProt	LLR -6.77	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 5,499 bp · p 0.00019 · regional, not allelic
Overall
CADD	32.0	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 0.00667% Admixed American · 4/59,966 alleles

Filtering AF 0.00538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00498%

Overall 0.00595% 96/1,613,850 alleles · very rare exomes 85/1,461,752 · genomes 11/152,098 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.016%	6,248
Admixed Americangrpmax	0.00667%	14,991
European (non-Finnish)	0.00661%	15,128
South Asian	0.00329%	30,352
African / African-American	0.00134%	74,898

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg16Cys
Coding: c.46C>T
MANE Select: NM_024025
Type: single nucleotide variant
Location: chr8:33597470 (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.Arg16His 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.Arg19Gln Uncertain significance ★ ⚠ same type
DUSP26 p.Arg19Trp 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-arg16cys (accessed [today's date]).

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