Is DUSP23 p.Val36Glu (c.107T>A) pathogenic?

DUSP23 p.Val36Glu (c.107T>A) is classified Uncertain significance in DUSP23 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). AlphaMissense: likely pathogenic (0.949); Very rare (popmax 0.00589%, amr).

How common is DUSP23 p.Val36Glu (c.107T>A) in the general population?

DUSP23 p.Val36Glu (c.107T>A) is very rare (popmax 0.00589%, amr) (gnomAD).

What do computational predictors say about DUSP23 p.Val36Glu (c.107T>A)?

AlphaMissense predicts likely pathogenic (score 0.949) — an in-silico prediction, not a clinical call.

DUSP23 p.Val36Glu

c.107T>A · VCV3274063

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.949 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00589%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.949	likely pathogenic
REVEL	0.892	moderately pathogenic-leaning
SaProt	LLR -16.07	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 1,234 bp · p 0.11 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 0.00589% Admixed American · 3/50,952 alleles

Filtering AF 0.00156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000833%

Overall 0.000194% 3/1,549,448 alleles · very rare exomes 3/1,397,116 · genomes 0/152,332 · joint denominator

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.Val36Glu
Coding: c.107T>A
MANE Select: NM_001319658
Type: single nucleotide variant
Location: chr1:159781207 (GRCh38)
Gene constraint: LOEUF 1.352 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.55 · 2 PDB
Residue 36: 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-val36glu (accessed [today's date]).

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