Is DUSP15 p.Arg217Ser (c.649C>A) pathogenic?

DUSP15 p.Arg217Ser (c.649C>A) is classified Uncertain significance in DUSP15 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-15). Very rare (popmax 0.00562%, amr).

How common is DUSP15 p.Arg217Ser (c.649C>A) in the general population?

DUSP15 p.Arg217Ser (c.649C>A) is very rare (popmax 0.00562%, amr) (gnomAD).

DUSP15 p.Arg217Ser

c.649C>A · VCV3505835

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00562%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.178	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 8,931 bp · p 0.015 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00562% Admixed American · 3/53,354 alleles

Filtering AF 0.00149% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000814%

Overall 0.000214% 3/1,400,742 alleles · very 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: DUSP15
Protein: p.Arg217Ser
Coding: c.649C>A
MANE Select: NM_080611
Type: single nucleotide variant
Location: chr20:31861462 (GRCh38)
Gene constraint: LOEUF 1.5 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.61 · 1 PDB

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-arg217ser (accessed [today's date]).

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