Is DUSP28 p.Leu79Pro (c.236T>C) pathogenic?

DUSP28 p.Leu79Pro (c.236T>C) is classified Uncertain significance in DUSP28 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-11). AlphaMissense: ambiguous (0.5439); Very rare (popmax 0.00429%, afr).

How common is DUSP28 p.Leu79Pro (c.236T>C) in the general population?

DUSP28 p.Leu79Pro (c.236T>C) is very rare (popmax 0.00429%, afr) (gnomAD).

What do computational predictors say about DUSP28 p.Leu79Pro (c.236T>C)?

AlphaMissense predicts ambiguous (score 0.5439) — an in-silico prediction, not a clinical call.

DUSP28 p.Leu79Pro

c.236T>C · rs1452894001 · VCV2536054

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5439 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00429%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.5439	ambiguous
REVEL	0.752	pathogenic-leaning
SaProt	LLR -11.34	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.2	GERP 1.3, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 779 bp · p 4.4e-10 · regional, not allelic
Overall
CADD	28.5	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 0.00429% African / African-American · 3/69,938 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000616%

Overall 0.000195% 3/1,536,402 alleles · very rare exomes 2/1,384,414 · genomes 1/151,988 · joint denominator

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.Leu79Pro
Coding: c.236T>C
MANE Select: NM_001370465
dbSNP: rs1452894001
Type: single nucleotide variant
Location: chr2:240560920 (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-leu79pro (accessed [today's date]).

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