Is DUSP28 p.Gln55Lys (c.163C>A) pathogenic?

DUSP28 p.Gln55Lys (c.163C>A) is classified Uncertain significance in DUSP28 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely pathogenic (0.7255); Very rare (popmax 0.00425%, nfe).

How common is DUSP28 p.Gln55Lys (c.163C>A) in the general population?

DUSP28 p.Gln55Lys (c.163C>A) is very rare (popmax 0.00425%, nfe) (gnomAD).

What do computational predictors say about DUSP28 p.Gln55Lys (c.163C>A)?

AlphaMissense predicts likely pathogenic (score 0.7255) — an in-silico prediction, not a clinical call.

DUSP28 p.Gln55Lys

c.163C>A · rs1047739442 · VCV2395174

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7255 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00425%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7255	likely pathogenic
REVEL	0.57	indeterminate
SaProt	LLR -8.45	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7	GERP 1.3, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 779 bp · p 4.4e-10 · regional, not allelic
Overall
CADD	25.7	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 0.00425% European (non-Finnish) · 46/1,083,080 alleles

Filtering AF 0.00325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00291%

Overall 0.00345% 48/1,391,494 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00425%	23,545
African / African-American	0.00303%	32,989

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.Gln55Lys
Coding: c.163C>A
MANE Select: NM_001282771 · reported on NM_001370465
dbSNP: rs1047739442
Type: single nucleotide variant
Location: chr2:240560847 (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-gln55lys (accessed [today's date]).

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