Is DUSP28 p.Pro24Thr (c.70C>A) pathogenic?

DUSP28 p.Pro24Thr (c.70C>A) is classified Uncertain significance in DUSP28 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: likely benign (0.2383); Very rare (popmax 0.00228%, amr).

How common is DUSP28 p.Pro24Thr (c.70C>A) in the general population?

DUSP28 p.Pro24Thr (c.70C>A) is very rare (popmax 0.00228%, amr) (gnomAD).

What do computational predictors say about DUSP28 p.Pro24Thr (c.70C>A)?

AlphaMissense predicts likely benign (score 0.2383) — an in-silico prediction, not a clinical call.

DUSP28 p.Pro24Thr

c.70C>A · rs2092915420 · VCV2547358

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2383 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00228%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2383	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -11.00	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.5	GERP 0.066, phastCons 0.99
Regional constraint	o/e 1.38	unconstrained · MANE · 779 bp · p 4.4e-10 · regional, not allelic
Overall
CADD	15.69	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00228% Admixed American · 1/43,764 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000267% 4/1,500,690 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00228%	43,764
African / African-American	0.00145%	68,916
European (non-Finnish)	0.000176%	568,353

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.Pro24Thr
Coding: c.70C>A
MANE Select: NM_001282771 · reported on NM_001370465
dbSNP: rs2092915420
Type: single nucleotide variant
Location: chr2:240560754 (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-pro24thr (accessed [today's date]).

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