Is DUSP7 p.Thr25Ile (c.74C>T) pathogenic?

DUSP7 p.Thr25Ile (c.74C>T) is classified Uncertain significance in DUSP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-12). AlphaMissense: likely benign (0.1519); Very rare (popmax 0.00051%, nfe).

How common is DUSP7 p.Thr25Ile (c.74C>T) in the general population?

DUSP7 p.Thr25Ile (c.74C>T) is very rare (popmax 0.00051%, nfe) (gnomAD).

What do computational predictors say about DUSP7 p.Thr25Ile (c.74C>T)?

AlphaMissense predicts likely benign (score 0.1519) — an in-silico prediction, not a clinical call.

DUSP7 p.Thr25Ile

c.74C>T · VCV4015458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1519 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00051%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1519	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -9.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP -1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 195 bp · p 0.91 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00051% European (non-Finnish) · 5/979,818 alleles

Filtering AF 0.00015% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000109%

Overall 0.00189% 23/1,215,612 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0857%	1,167
Remaining individualsnot grpmax-eligible	0.00912%	10,967
European (non-Finnish)grpmax	0.00051%	195,964

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: DUSP7
Protein: p.Thr25Ile
Coding: c.74C>T
MANE Select: NM_001947
Type: single nucleotide variant
Location: chr3:52056293 (GRCh38)
Gene constraint: LOEUF 0.547 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 76.02 · 1 PDB
Residue 25: the 'disordered' region

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-thr25ile (accessed [today's date]).

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