Is DUSP23 p.Phe99Cys (c.296T>G) pathogenic?

DUSP23 p.Phe99Cys (c.296T>G) is classified Uncertain significance in DUSP23 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-29). AlphaMissense: ambiguous (0.4388); Very rare (popmax 0.0011%, sas).

How common is DUSP23 p.Phe99Cys (c.296T>G) in the general population?

DUSP23 p.Phe99Cys (c.296T>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DUSP23 p.Phe99Cys (c.296T>G)?

AlphaMissense predicts ambiguous (score 0.4388) — an in-silico prediction, not a clinical call.

DUSP23 p.Phe99Cys

c.296T>G · rs1413081919 · VCV2279976

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4388 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
AlphaMissense	0.4388	ambiguous
REVEL	0.422	indeterminate
SaProt	LLR -7.01	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP -0.54, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 1,234 bp · p 0.11 · regional, not allelic
Overall
CADD	24.3	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 0.0011% South Asian · 1/91,074 alleles

Overall 0.000137% 2/1,461,858 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,508
South Asiangrpmax	0.0011%	91,074

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe99Cys
Coding: c.296T>G
MANE Select: NM_001319658
dbSNP: rs1413081919
Type: single nucleotide variant
Location: chr1:159782181 (GRCh38)
Gene constraint: LOEUF 1.352 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.55 · 2 PDB
Residue 99: 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-phe99cys (accessed [today's date]).

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