Is DUSP15 p.Arg78His (c.233G>A) pathogenic?

DUSP15 p.Arg78His (c.233G>A) is classified Uncertain significance in DUSP15 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-31). AlphaMissense: likely pathogenic (0.8511); Very rare (popmax 0.00305%, nfe).

How common is DUSP15 p.Arg78His (c.233G>A) in the general population?

DUSP15 p.Arg78His (c.233G>A) is very rare (popmax 0.00305%, nfe) (gnomAD).

What do computational predictors say about DUSP15 p.Arg78His (c.233G>A)?

AlphaMissense predicts likely pathogenic (score 0.8511) — an in-silico prediction, not a clinical call.

DUSP15 p.Arg78His

c.233G>A · VCV3842895

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8511 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00305%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8511	likely pathogenic
REVEL	0.461	indeterminate
SaProt	LLR -12.09	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 8,931 bp · p 0.015 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 R75H vs ClinVar R78H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00305% European (non-Finnish) · 36/1,179,962 alleles

Filtering AF 0.00223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00198%

Overall 0.00378% 61/1,613,878 alleles · very rare exomes 52/1,461,792 · genomes 9/152,086 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0608%	1,645
Remaining individualsnot grpmax-eligible	0.0064%	15,621
European (non-Finnish)grpmax	0.00305%	32,777
South Asian	0.0022%	45,537
Admixed American	0.00167%	60,000

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg78His
Coding: c.233G>A
MANE Select: NM_080611
Type: single nucleotide variant
Location: chr20:31863937 (GRCh38)
Gene constraint: LOEUF 1.5 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.61 · 1 PDB
Residue 75 UniProt numbering: the tyrosine-protein phosphatase domain; an α-helix

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-arg78his (accessed [today's date]).

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