Is DUSP7 p.Thr180Arg (c.539C>G) pathogenic?

DUSP7 p.Thr180Arg (c.539C>G) is classified Uncertain significance in DUSP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-02). AlphaMissense: likely benign (0.1691); Very rare (popmax 0.000439%, nfe).

How common is DUSP7 p.Thr180Arg (c.539C>G) in the general population?

DUSP7 p.Thr180Arg (c.539C>G) is very rare (popmax 0.000439%, nfe) (gnomAD).

What do computational predictors say about DUSP7 p.Thr180Arg (c.539C>G)?

AlphaMissense predicts likely benign (score 0.1691) — an in-silico prediction, not a clinical call.

DUSP7 p.Thr180Arg

c.539C>G · VCV3505925

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1691 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000439%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1691	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -4.63	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 7.6	GERP 0.98, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 5,068 bp · p 3.9e-13 · regional, not allelic
Overall
CADD	22.7	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 0.000439% European (non-Finnish) · 5/1,138,598 alleles

Filtering AF 0.000129% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.4e-05%

Overall 0.000327% 5/1,529,522 alleles · very rare exomes 5/1,377,172 · genomes 0/152,350 · joint denominator

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.Thr180Arg
Coding: c.539C>G
MANE Select: NM_001947
Type: single nucleotide variant
Location: chr3:52054353 (GRCh38)
Gene constraint: LOEUF 0.547 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 76.02 · 1 PDB
Residue 180: the rhodanese domain

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

Similar variants

DUSP7 p.Thr180Ile Uncertain significance ★ ⚠ same residue
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

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-thr180arg (accessed [today's date]).

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