Is DUSP28 p.Asp73His (c.217G>C) pathogenic?

DUSP28 p.Asp73His (c.217G>C) is classified Uncertain significance in DUSP28 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-12). AlphaMissense: likely pathogenic (0.5988); Very rare (popmax 0.00271%, eas).

How common is DUSP28 p.Asp73His (c.217G>C) in the general population?

DUSP28 p.Asp73His (c.217G>C) is very rare (popmax 0.00271%, eas) (gnomAD).

What do computational predictors say about DUSP28 p.Asp73His (c.217G>C)?

AlphaMissense predicts likely pathogenic (score 0.5988) — an in-silico prediction, not a clinical call.

DUSP28 p.Asp73His

c.217G>C · VCV3505888

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5988 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5988	likely pathogenic
REVEL	0.196	benign-leaning
SaProt	LLR -8.94	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 1.3, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 779 bp · p 4.4e-10 · regional, not allelic
Overall
CADD	29.5	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 0.00271% East Asian · 1/36,950 alleles

Filtering AF 0.000631% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000486%

Overall 0.00125% 19/1,523,276 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0051%	19,609
East Asiangrpmax	0.00271%	36,950
Admixed American	0.0021%	47,602
South Asian	0.00121%	82,906
European (non-Finnish)	0.00113%	88,394

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp73His
Coding: c.217G>C
MANE Select: NM_001282771 · reported on NM_001370465
Type: single nucleotide variant
Location: chr2:240560901 (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-asp73his (accessed [today's date]).

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