Is DUSP15 p.Asp47Gly (c.140A>G) pathogenic?

DUSP15 p.Asp47Gly (c.140A>G) is classified Uncertain significance in DUSP15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-06). AlphaMissense: likely benign (0.1467); Very rare (popmax 0.00627%, nfe).

How common is DUSP15 p.Asp47Gly (c.140A>G) in the general population?

DUSP15 p.Asp47Gly (c.140A>G) is very rare (popmax 0.00627%, nfe) (gnomAD).

What do computational predictors say about DUSP15 p.Asp47Gly (c.140A>G)?

AlphaMissense predicts likely benign (score 0.1467) — an in-silico prediction, not a clinical call.

DUSP15 p.Asp47Gly

c.140A>G · VCV3842894

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1467 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00627%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1467	likely benign
REVEL	0.144	moderately benign-leaning
SaProt	LLR -4.07	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 3.5	GERP 0.91, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 8,931 bp · p 0.015 · regional, not allelic
Overall
CADD	18.8	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D44G vs ClinVar D47G) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00627% European (non-Finnish) · 74/1,179,990 alleles

Filtering AF 0.00511% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00459% 74/1,613,864 alleles · very rare exomes 71/1,461,826 · genomes 3/152,038 · 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: DUSP15
Protein: p.Asp47Gly
Coding: c.140A>G
MANE Select: NM_080611
Type: single nucleotide variant
Location: chr20:31865001 (GRCh38)
Gene constraint: LOEUF 1.5 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.61 · 1 PDB
Residue 44 UniProt numbering: the tyrosine-protein phosphatase domain

Full DUSP15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP15 p.Ala191Pro Uncertain significance ★ same type
DUSP15 p.Ala192Pro Uncertain significance ★ same type
DUSP15 p.Arg148Gln Uncertain significance ★ same type
DUSP15 p.Arg166Ser Uncertain significance ★ same type
DUSP15 p.Arg174Cys Uncertain significance ★ same type
DUSP15 p.Arg174His Uncertain significance ★ same type
DUSP15 p.Arg176Pro Uncertain significance ★ same type
DUSP15 p.Arg176Trp 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/dusp15-p-asp47gly (accessed [today's date]).

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