Is DUSP28 p.Ser13Leu (c.38C>T) pathogenic?

DUSP28 p.Ser13Leu (c.38C>T) is classified Uncertain significance in DUSP28 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-27). AlphaMissense: likely benign (0.1397); Ultra-rare (popmax 0.0221%, nfe).

How common is DUSP28 p.Ser13Leu (c.38C>T) in the general population?

DUSP28 p.Ser13Leu (c.38C>T) is ultra-rare (popmax 0.0221%, nfe) (gnomAD).

What do computational predictors say about DUSP28 p.Ser13Leu (c.38C>T)?

AlphaMissense predicts likely benign (score 0.1397) — an in-silico prediction, not a clinical call.

DUSP28 p.Ser13Leu

c.38C>T · rs778568184 · VCV2386645

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1397 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0221%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1397	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -6.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.73	GERP -1.9
Regional constraint	o/e 1.38	unconstrained · MANE · 779 bp · p 4.4e-10 · regional, not allelic
Overall
CADD	0.165	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 0.0221% European (non-Finnish) · 254/1,148,230 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0189%

Overall 0.0172% 262/1,524,812 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0221%	4,521
Remaining individualsnot grpmax-eligible	0.0068%	14,699
African / African-American	0.00431%	23,215
Admixed American	0.00208%	47,996

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.Ser13Leu
Coding: c.38C>T
MANE Select: NM_001282771 · reported on NM_001370465
dbSNP: rs778568184
Type: single nucleotide variant
Location: chr2:240560722 (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-ser13leu (accessed [today's date]).

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