Is DUSP28 p.Arg120Gln (c.359G>A) pathogenic?

DUSP28 p.Arg120Gln (c.359G>A) is classified Uncertain significance in DUSP28 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-21). AlphaMissense: likely benign (0.1945); Ultra-rare (popmax 0.0472%, mid).

How common is DUSP28 p.Arg120Gln (c.359G>A) in the general population?

DUSP28 p.Arg120Gln (c.359G>A) is ultra-rare (popmax 0.0472%, mid) (gnomAD).

What do computational predictors say about DUSP28 p.Arg120Gln (c.359G>A)?

AlphaMissense predicts likely benign (score 0.1945) — an in-silico prediction, not a clinical call.

DUSP28 p.Arg120Gln

c.359G>A · rs537091038 · VCV2208451

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1945 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0472%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1945	likely benign
REVEL	0.508	indeterminate
SaProt	LLR -8.66	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.1	GERP 1.3, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 779 bp · p 4.4e-10 · regional, not allelic
Overall
CADD	24.8	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0472% Middle Eastern · 2/4,240 alleles

Filtering AF 0.0117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00937%

Overall 0.00171% 26/1,516,990 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0472%	2,120
African / African-American	0.0194%	5,151
East Asian	0.0144%	6,941
Remaining individualsnot grpmax-eligible	0.00171%	58,634
European (non-Finnish)	0.000263%	380,690

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: DUSP28
Protein: p.Arg120Gln
Coding: c.359G>A
MANE Select: NM_001282771 · reported on NM_001370465
dbSNP: rs537091038
Type: single nucleotide variant
Location: chr2:240561043 (GRCh38)

Full DUSP28 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/dusp28-p-arg120gln (accessed [today's date]).

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