Is DUSP2 p.Leu67Phe (c.199C>T) pathogenic?

DUSP2 p.Leu67Phe (c.199C>T) is classified Uncertain significance in DUSP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely benign (0.3139); Ultra-rare (popmax 0.032%, eas).

How common is DUSP2 p.Leu67Phe (c.199C>T) in the general population?

DUSP2 p.Leu67Phe (c.199C>T) is ultra-rare (popmax 0.032%, eas) (gnomAD).

What do computational predictors say about DUSP2 p.Leu67Phe (c.199C>T)?

AlphaMissense predicts likely benign (score 0.3139) — an in-silico prediction, not a clinical call.

DUSP2 p.Leu67Phe

c.199C>T · VCV4245530

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3139 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3139	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -11.03	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 0.58, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 1,528 bp · p 0.41 · regional, not allelic
Overall
CADD	22.4	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 0.032% East Asian · 10/31,282 alleles

Filtering AF 0.0173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0132%

Overall 0.00364% 48/1,319,390 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.032%	3,128
Remaining individualsnot grpmax-eligible	0.0061%	16,403
South Asian	0.00424%	23,566
European (non-Finnish)	0.00307%	32,526
African / African-American	0.00155%	64,566

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: DUSP2
Protein: p.Leu67Phe
Coding: c.199C>T
MANE Select: NM_004418
Type: single nucleotide variant
Location: chr2:96145156 (GRCh38)
Gene constraint: LOEUF 1.442 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.59 · 1 PDB
Residue 67: the rhodanese domain

Full DUSP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP2 p.Ala107Val Uncertain significance ★ ⚠ same type
DUSP2 p.Ala265Pro Uncertain significance ★ ⚠ same type
DUSP2 p.Ala265Val Uncertain significance ★ ⚠ same type
DUSP2 p.Ala45Val Uncertain significance ★ ⚠ same type
DUSP2 p.Ala65Gly Uncertain significance ★ ⚠ same type
DUSP2 p.Arg263Cys Uncertain significance ★ ⚠ same type
DUSP2 p.Arg26His Uncertain significance ★ ⚠ same type
DUSP2 p.Arg26Ser 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/dusp2-p-leu67phe (accessed [today's date]).

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