Is DUSP1 p.Leu109Phe (c.325C>T) pathogenic?

DUSP1 p.Leu109Phe (c.325C>T) is classified Uncertain significance in DUSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). AlphaMissense: likely pathogenic (0.7487); Very rare (popmax 0.00742%, amr).

How common is DUSP1 p.Leu109Phe (c.325C>T) in the general population?

DUSP1 p.Leu109Phe (c.325C>T) is very rare (popmax 0.00742%, amr) (gnomAD).

What do computational predictors say about DUSP1 p.Leu109Phe (c.325C>T)?

AlphaMissense predicts likely pathogenic (score 0.7487) — an in-silico prediction, not a clinical call.

DUSP1 p.Leu109Phe

c.325C>T · rs923998270 · VCV3086234

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7487 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00742%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7487	likely pathogenic
REVEL	0.407	indeterminate
SaProt	LLR -9.88	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,309 bp · p 0.037 · regional, not allelic
Overall
CADD	25.0	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 0.00742% Admixed American · 2/26,950 alleles

Filtering AF 0.00123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000459%

Overall 0.000379% 5/1,318,046 alleles · very rare exomes 5/1,165,986 · genomes 0/152,060 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00742%	13,475
Remaining individualsnot grpmax-eligible	0.00201%	49,676
European (non-Finnish)	0.000192%	520,679

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: DUSP1
Protein: p.Leu109Phe
Coding: c.325C>T
MANE Select: NM_004417
dbSNP: rs923998270
Type: single nucleotide variant
Location: chr5:172770628 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI 0.33 (gnomAD)
Structure: AlphaFold pLDDT 80.09 · 4 PDB
Residue 109: the rhodanese domain

Full DUSP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP1 p.Ala103Val Uncertain significance ★ ⚠ same type
DUSP1 p.Ala113Gly Uncertain significance ★ ⚠ same type
DUSP1 p.Ala197Ser Uncertain significance ★ ⚠ same type
DUSP1 p.Ala197Thr Uncertain significance ★ ⚠ same type
DUSP1 p.Ala202Thr Uncertain significance ★ ⚠ same type
DUSP1 p.Ala59Ser Uncertain significance ★ ⚠ same type
DUSP1 p.Ala69Thr Uncertain significance ★ ⚠ same type
DUSP1 p.Ala92Asp 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/dusp1-p-leu109phe (accessed [today's date]).

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