Is DUSP15 p.Lys235Arg (c.704A>G) pathogenic?

DUSP15 p.Lys235Arg (c.704A>G) is classified Uncertain significance in DUSP15 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-23). Very rare (popmax 0.000258%, nfe).

How common is DUSP15 p.Lys235Arg (c.704A>G) in the general population?

DUSP15 p.Lys235Arg (c.704A>G) is very rare (popmax 0.000258%, nfe) (gnomAD).

DUSP15 p.Lys235Arg

c.704A>G · rs2515530106 · VCV2488763

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000258%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.036	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.65	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 7.4	GERP 2.1, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 8,931 bp · p 0.015 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000258% European (non-Finnish) · 3/1,161,090 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000193% 3/1,555,410 alleles · very rare exomes 3/1,403,084 · genomes 0/152,326 · 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.Lys235Arg
Coding: c.704A>G
MANE Select: NM_080611
dbSNP: rs2515530106
Type: single nucleotide variant
Location: chr20:31861407 (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-lys235arg (accessed [today's date]).

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