Is DUSP7 p.Phe360Leu (c.1078T>C) pathogenic?

DUSP7 p.Phe360Leu (c.1078T>C) is classified Uncertain significance in DUSP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-13). AlphaMissense: likely pathogenic (0.9174); Ultra-rare (popmax 0.0254%, afr).

How common is DUSP7 p.Phe360Leu (c.1078T>C) in the general population?

DUSP7 p.Phe360Leu (c.1078T>C) is ultra-rare (popmax 0.0254%, afr) (gnomAD).

What do computational predictors say about DUSP7 p.Phe360Leu (c.1078T>C)?

AlphaMissense predicts likely pathogenic (score 0.9174) — an in-silico prediction, not a clinical call.

DUSP7 p.Phe360Leu

c.1078T>C · VCV3274093

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9174 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0254%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9174	likely pathogenic
REVEL	0.414	indeterminate
SaProt	LLR -4.86	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP -0.094, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 214 bp · p 0.041 · regional, not allelic
Overall
CADD	22.8	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 0.0254% African / African-American · 19/74,948 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00118% 19/1,614,136 alleles · ultra-rare

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: DUSP7
Protein: p.Phe360Leu
Coding: c.1078T>C
MANE Select: NM_001947
Type: single nucleotide variant
Location: chr3:52050997 (GRCh38)
Gene constraint: LOEUF 0.547 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 76.02 · 1 PDB
Residue 360: the tyrosine-protein phosphatase domain; an α-helix

Full DUSP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP7 p.Ala125Val Uncertain significance ★ ⚠ same type
DUSP7 p.Ala243Asp Uncertain significance ★ ⚠ same type
DUSP7 p.Arg11Pro Uncertain significance ★ ⚠ same type
DUSP7 p.Arg211Cys Uncertain significance ★ ⚠ same type
DUSP7 p.Arg26Gln Uncertain significance ★ ⚠ same type
DUSP7 p.Asn176Ser Uncertain significance ★ ⚠ same type
DUSP7 p.Cys391Arg Uncertain significance ★ same type
DUSP7 p.Gln167Glu 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/dusp7-p-phe360leu (accessed [today's date]).

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