Is DUSP21 p.Leu104Pro (c.311T>C) pathogenic?

DUSP21 p.Leu104Pro (c.311T>C) is classified Uncertain significance in DUSP21 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-08). AlphaMissense: likely pathogenic (0.963); Absent from gnomAD v4.1.

How common is DUSP21 p.Leu104Pro (c.311T>C) in the general population?

DUSP21 p.Leu104Pro (c.311T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUSP21 p.Leu104Pro (c.311T>C)?

AlphaMissense predicts likely pathogenic (score 0.963) — an in-silico prediction, not a clinical call.

DUSP21 p.Leu104Pro

c.311T>C · rs2519175176 · VCV2323577

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.963 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.963	likely pathogenic · top 7% in DUSP21
REVEL	0.517	indeterminate
SaProt	LLR -11.43	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 1.9, phastCons 0.97
Regional constraint	o/e 0.94	unconstrained · MANE · 569 bp · p 0.45 · regional, not allelic
Overall
CADD	23.9	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

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.Leu104Pro
Coding: c.311T>C
MANE Select: NM_022076
dbSNP: rs2519175176
Type: single nucleotide variant
Location: chrX:44844443 (GRCh38)
Structure: AlphaFold pLDDT 92.15
Residue 104: the tyrosine-protein phosphatase domain; the 'sufficient for mitochondrial localization' region

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-leu104pro (accessed [today's date]).

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