Is DUSP23 p.Arg87Trp (c.259C>T) pathogenic?

DUSP23 p.Arg87Trp (c.259C>T) is classified Uncertain significance in DUSP23 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-04). AlphaMissense: likely benign (0.2106); Very rare (popmax 0.0042%, afr).

How common is DUSP23 p.Arg87Trp (c.259C>T) in the general population?

DUSP23 p.Arg87Trp (c.259C>T) is very rare (popmax 0.0042%, afr) (gnomAD).

What do computational predictors say about DUSP23 p.Arg87Trp (c.259C>T)?

AlphaMissense predicts likely benign (score 0.2106) — an in-silico prediction, not a clinical call.

DUSP23 p.Arg87Trp

c.259C>T · VCV3505881

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2106 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0042%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2106	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -12.75	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.017	GERP 0.98, phastCons 0.001
Regional constraint	o/e 1.11	unconstrained · MANE · 1,234 bp · p 0.11 · regional, not allelic
Overall
CADD	24.2	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 0.0042% African / African-American · 3/71,374 alleles

Filtering AF 0.00112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000609%

Overall 0.000198% 3/1,514,504 alleles · very rare

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: DUSP23
Protein: p.Arg87Trp
Coding: c.259C>T
MANE Select: NM_001319658
Type: single nucleotide variant
Location: chr1:159781359 (GRCh38)
Gene constraint: LOEUF 1.352 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.55 · 2 PDB
Residue 87: the tyrosine-protein phosphatase domain

Full DUSP23 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP23 p.Arg87Leu Uncertain significance ★ ⚠ same residue
DUSP23 p.Arg114Gln Uncertain significance ★ ⚠ same type
DUSP23 p.Arg129Pro Uncertain significance ★ ⚠ same type
DUSP23 p.Asn7Thr Uncertain significance ★ ⚠ same type
DUSP23 p.Asn85Ser Uncertain significance ★ ⚠ same type
DUSP23 p.Cys67Arg Uncertain significance ★ ⚠ same type
DUSP23 p.Cys67Phe Uncertain significance ★ ⚠ same type
DUSP23 p.Gln138Arg 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/dusp23-p-arg87trp (accessed [today's date]).

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