Is DUSP28 p.Ala41Gly (c.122C>G) pathogenic?

DUSP28 p.Ala41Gly (c.122C>G) is classified Uncertain significance in DUSP28 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-16). AlphaMissense: likely benign (0.0786); Very rare (popmax 0.000181%, nfe).

How common is DUSP28 p.Ala41Gly (c.122C>G) in the general population?

DUSP28 p.Ala41Gly (c.122C>G) is very rare (popmax 0.000181%, nfe) (gnomAD).

What do computational predictors say about DUSP28 p.Ala41Gly (c.122C>G)?

AlphaMissense predicts likely benign (score 0.0786) — an in-silico prediction, not a clinical call.

DUSP28 p.Ala41Gly

c.122C>G · rs1189324201 · VCV3086305

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0786 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000181%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0786	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -7.50	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -3	GERP -2.4
Regional constraint	o/e 1.38	unconstrained · MANE · 779 bp · p 4.4e-10 · regional, not allelic
Overall
CADD	4.416	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 0.000181% European (non-Finnish) · 2/1,105,502 alleles

Filtering AF 3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000139% 2/1,441,816 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: DUSP28
Protein: p.Ala41Gly
Coding: c.122C>G
MANE Select: NM_001282771 · reported on NM_001370465
dbSNP: rs1189324201
Type: single nucleotide variant
Location: chr2:240560806 (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-ala41gly (accessed [today's date]).

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