Is DUSP28 p.Ala91Thr (c.271G>A) pathogenic?

DUSP28 p.Ala91Thr (c.271G>A) is classified Uncertain significance in DUSP28 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-04). AlphaMissense: likely benign (0.107); Very rare (popmax 0.00121%, sas).

How common is DUSP28 p.Ala91Thr (c.271G>A) in the general population?

DUSP28 p.Ala91Thr (c.271G>A) is very rare (popmax 0.00121%, sas) (gnomAD).

What do computational predictors say about DUSP28 p.Ala91Thr (c.271G>A)?

AlphaMissense predicts likely benign (score 0.107) — an in-silico prediction, not a clinical call.

DUSP28 p.Ala91Thr

c.271G>A · VCV3505891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.107 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00121%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.107	likely benign
REVEL	0.32	indeterminate
SaProt	LLR -9.37	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 7.8	GERP 1.3, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 779 bp · p 4.4e-10 · regional, not allelic
Overall
CADD	22.5	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 0.00121% South Asian · 1/82,938 alleles

Overall 0.000132% 2/1,520,676 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00121%	82,938
European (non-Finnish)	8.71e-05%	1,147,644

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.Ala91Thr
Coding: c.271G>A
MANE Select: NM_001282771 · reported on NM_001370465
Type: single nucleotide variant
Location: chr2:240560955 (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-ala91thr (accessed [today's date]).

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