Is DUSP28 p.Ala12Thr (c.34G>A) pathogenic?

DUSP28 p.Ala12Thr (c.34G>A) is classified Uncertain significance in DUSP28 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-22). AlphaMissense: likely benign (0.1002); Very rare (popmax 0.0012%, sas).

How common is DUSP28 p.Ala12Thr (c.34G>A) in the general population?

DUSP28 p.Ala12Thr (c.34G>A) is very rare (popmax 0.0012%, sas) (gnomAD).

What do computational predictors say about DUSP28 p.Ala12Thr (c.34G>A)?

AlphaMissense predicts likely benign (score 0.1002) — an in-silico prediction, not a clinical call.

DUSP28 p.Ala12Thr

c.34G>A · rs2092910857 · VCV3086309

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1002 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0012%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1002	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -8.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.34	GERP -2.1
Regional constraint	o/e 1.38	unconstrained · MANE · 779 bp · p 4.4e-10 · regional, not allelic
Overall
CADD	7.313	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 0.0012% South Asian · 1/83,190 alleles

Overall 0.000131% 2/1,524,916 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0012%	83,190
European (non-Finnish)	8.71e-05%	1,148,244

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.Ala12Thr
Coding: c.34G>A
MANE Select: NM_001282771 · reported on NM_001370465
dbSNP: rs2092910857
Type: single nucleotide variant
Location: chr2:240560718 (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-ala12thr (accessed [today's date]).

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