Is DUSP1 p.Phe243Tyr (c.728T>A) pathogenic?

DUSP1 p.Phe243Tyr (c.728T>A) is classified Uncertain significance in DUSP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: ambiguous (0.5096); Very rare (popmax 0.000254%, nfe).

How common is DUSP1 p.Phe243Tyr (c.728T>A) in the general population?

DUSP1 p.Phe243Tyr (c.728T>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about DUSP1 p.Phe243Tyr (c.728T>A)?

AlphaMissense predicts ambiguous (score 0.5096) — an in-silico prediction, not a clinical call.

DUSP1 p.Phe243Tyr

c.728T>A · VCV4015358

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5096 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5096	ambiguous
REVEL	0.743	pathogenic-leaning
SaProt	LLR -7.83	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.54	unconstrained · MANE · 701 bp · p 2.1e-06 · regional, not allelic
Overall
CADD	24.1	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 0.000254% European (non-Finnish) · 3/1,180,044 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,461,892 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
European (non-Finnish)grpmax	0.000254%	393,348

Ashkenazi Jewish 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: DUSP1
Protein: p.Phe243Tyr
Coding: c.728T>A
MANE Select: NM_004417
Type: single nucleotide variant
Location: chr5:172769580 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI 0.33 (gnomAD)
Structure: AlphaFold pLDDT 80.09 · 4 PDB
Residue 243: an α-helix; the tyrosine-protein phosphatase 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-phe243tyr (accessed [today's date]).

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