Is DUSP21 p.Leu42Phe (c.124C>T) pathogenic?

DUSP21 p.Leu42Phe (c.124C>T) is classified Uncertain significance in DUSP21 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-26). AlphaMissense: likely benign (0.182); Absent from gnomAD v4.1.

How common is DUSP21 p.Leu42Phe (c.124C>T) in the general population?

DUSP21 p.Leu42Phe (c.124C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP21 p.Leu42Phe (c.124C>T)?

AlphaMissense predicts likely benign (score 0.182) — an in-silico prediction, not a clinical call.

DUSP21 p.Leu42Phe

c.124C>T · rs2519174882 · VCV2540748

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.182 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.182	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -4.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3	GERP -4.1
Regional constraint	o/e 0.94	unconstrained · MANE · 569 bp · p 0.45 · regional, not allelic
Overall
CADD	0.049	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

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: DUSP21
Protein: p.Leu42Phe
Coding: c.124C>T
MANE Select: NM_022076
dbSNP: rs2519174882
Type: single nucleotide variant
Location: chrX:44844256 (GRCh38)
Structure: AlphaFold pLDDT 92.15
Residue 42: the tyrosine-protein phosphatase domain

Full DUSP21 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP21 p.Ala132Thr Uncertain significance ★ ⚠ same type
DUSP21 p.Ala5Thr Uncertain significance ★ ⚠ same type
DUSP21 p.Arg140His Uncertain significance ★ ⚠ same type
DUSP21 p.Asp178Gly Uncertain significance ★ ⚠ same type
DUSP21 p.Asp75Asn Uncertain significance ★ ⚠ same type
DUSP21 p.Gln152Arg Uncertain significance ★ ⚠ same type
DUSP21 p.Gln15His Uncertain significance ★ ⚠ same type
DUSP21 p.Gly13Ser 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/dusp21-p-leu42phe (accessed [today's date]).

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