Is DUSP7 p.Ser396Leu (c.1187C>T) pathogenic?

DUSP7 p.Ser396Leu (c.1187C>T) is classified Uncertain significance in DUSP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0759); Very rare (popmax 0.00966%, nfe).

How common is DUSP7 p.Ser396Leu (c.1187C>T) in the general population?

DUSP7 p.Ser396Leu (c.1187C>T) is very rare (popmax 0.00966%, nfe) (gnomAD).

What do computational predictors say about DUSP7 p.Ser396Leu (c.1187C>T)?

AlphaMissense predicts likely benign (score 0.0759) — an in-silico prediction, not a clinical call.

DUSP7 p.Ser396Leu

c.1187C>T · rs754356172 · VCV2404752

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0759 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00966%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0759	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -7.90	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 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 214 bp · p 0.041 · regional, not allelic
Overall
CADD	21.7	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 0.00966% European (non-Finnish) · 114/1,180,054 alleles

Filtering AF 0.00817% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00761%

Overall 0.00762% 123/1,614,128 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00966%	10,351
Remaining individualsnot grpmax-eligible	0.0064%	15,621
South Asian	0.00329%	30,364
East Asian	0.00223%	44,900
African / African-American	0.00133%	74,946

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.Ser396Leu
Coding: c.1187C>T
MANE Select: NM_001947
dbSNP: rs754356172
Type: single nucleotide variant
Location: chr3:52050888 (GRCh38)
Gene constraint: LOEUF 0.547 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 76.02 · 1 PDB

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-ser396leu (accessed [today's date]).

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