Is DUSP23 p.Ile80Ser (c.239T>G) pathogenic?

DUSP23 p.Ile80Ser (c.239T>G) is classified Uncertain significance in DUSP23 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: likely pathogenic (0.7528); Absent from gnomAD v4.1.

How common is DUSP23 p.Ile80Ser (c.239T>G) in the general population?

DUSP23 p.Ile80Ser (c.239T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP23 p.Ile80Ser (c.239T>G)?

AlphaMissense predicts likely pathogenic (score 0.7528) — an in-silico prediction, not a clinical call.

DUSP23 p.Ile80Ser

c.239T>G · VCV3505883

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7528 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7528	likely pathogenic
REVEL	0.527	indeterminate
SaProt	LLR -12.64	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.95, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 1,234 bp · p 0.11 · regional, not allelic
Overall
CADD	29.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DUSP23
Protein: p.Ile80Ser
Coding: c.239T>G
MANE Select: NM_001319658
Type: single nucleotide variant
Location: chr1:159781339 (GRCh38)
Gene constraint: LOEUF 1.352 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.55 · 2 PDB
Residue 80: an α-helix; the tyrosine-protein phosphatase domain

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

Similar variants

DUSP23 p.Arg114Gln Uncertain significance ★ ⚠ same type
DUSP23 p.Arg129Pro Uncertain significance ★ ⚠ same type
DUSP23 p.Arg87Leu Uncertain significance ★ ⚠ same type
DUSP23 p.Arg87Trp 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

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-ile80ser (accessed [today's date]).

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