Is DUSP23 p.Leu34Val (c.100C>G) pathogenic?

DUSP23 p.Leu34Val (c.100C>G) is classified Uncertain significance in DUSP23 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-18). AlphaMissense: likely benign (0.0959); Rare (popmax 0.615%, nfe).

How common is DUSP23 p.Leu34Val (c.100C>G) in the general population?

DUSP23 p.Leu34Val (c.100C>G) is rare (popmax 0.615%, nfe) (gnomAD).

What do computational predictors say about DUSP23 p.Leu34Val (c.100C>G)?

AlphaMissense predicts likely benign (score 0.0959) — an in-silico prediction, not a clinical call.

DUSP23 p.Leu34Val

c.100C>G · rs199665962 · VCV2410173

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0959 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.615%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0959	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -6.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1	GERP -1.4
Regional constraint	o/e 1.11	unconstrained · MANE · 1,234 bp · p 0.11 · regional, not allelic
Overall
CADD	14.94	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.615% European (non-Finnish) · 7,053/1,146,514 alleles

Filtering AF 0.603% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.598%

Overall 0.497% 7,694/1,549,534 alleles · rare exomes 7,219/1,397,170 · genomes 475/152,364 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.615%	163
Remaining individualsnot grpmax-eligible	0.523%	191
Admixed American	0.253%	395
South Asian	0.114%	875
African / African-American	0.0821%	1,219
Middle Eastern	0.0521%	1,921
Finnishnot grpmax-eligible	0.0476%	2,099
Ashkenazi Jewishnot grpmax-eligible	0.0385%	2,599

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.Leu34Val
Coding: c.100C>G
MANE Select: NM_001319658
dbSNP: rs199665962
Type: single nucleotide variant
Location: chr1:159781200 (GRCh38)
Gene constraint: LOEUF 1.352 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.55 · 2 PDB
Residue 34: 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-leu34val (accessed [today's date]).

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