Is DUSP23 p.Leu56Val (c.166C>G) pathogenic?

DUSP23 p.Leu56Val (c.166C>G) is classified Uncertain significance in DUSP23 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-06). AlphaMissense: likely benign (0.1848); Absent from gnomAD v4.1.

How common is DUSP23 p.Leu56Val (c.166C>G) in the general population?

DUSP23 p.Leu56Val (c.166C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP23 p.Leu56Val (c.166C>G)?

AlphaMissense predicts likely benign (score 0.1848) — an in-silico prediction, not a clinical call.

DUSP23 p.Leu56Val

c.166C>G · rs2525790580 · VCV2234891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1848 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1848	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -10.19	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 7.5	GERP 1.8, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 1,234 bp · p 0.11 · regional, not allelic
Overall
CADD	21.8	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

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.Leu56Val
Coding: c.166C>G
MANE Select: NM_001319658
dbSNP: rs2525790580
Type: single nucleotide variant
Location: chr1:159781266 (GRCh38)
Gene constraint: LOEUF 1.352 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.55 · 2 PDB
Residue 56: a β-strand; 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-leu56val (accessed [today's date]).

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