Is DUSP4 p.His191= (c.573C>T) pathogenic?

DUSP4 p.His191= (c.573C>T) is classified Likely benign in DUSP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-01). Rare (popmax 0.363%, nfe).

How common is DUSP4 p.His191= (c.573C>T) in the general population?

DUSP4 p.His191= (c.573C>T) is rare (popmax 0.363%, nfe) (gnomAD).

DUSP4 p.His191=

c.573C>T · rs41277861 · VCV2658512

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.363%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.9	GERP -3.4
Overall
CADD	0.116	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.363% European (non-Finnish) · 4,201/1,158,038 alleles

Filtering AF 0.354% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.35%

Overall 0.309% 4,851/1,571,422 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.43%	70
European (non-Finnish)grpmax	0.363%	276
East Asian	0.356%	281
Remaining individualsnot grpmax-eligible	0.289%	346
South Asian	0.188%	533
Admixed American	0.127%	790
Ashkenazi Jewishnot grpmax-eligible	0.114%	875
African / African-American	0.054%	1,853
Middle Eastern	0.018%	5,556
Finnishnot grpmax-eligible	0.00981%	10,194

Amish 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: DUSP4
Protein: p.His191=
Coding: c.573C>T
MANE Select: NM_001394
dbSNP: rs41277861
Type: single nucleotide variant
Location: chr8:29340104 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 78.78 · 1 PDB

Full DUSP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP4 p.Ala163Gly Uncertain significance ★ ⚠ same type
DUSP4 p.Ala166Thr Uncertain significance ★ ⚠ same type
DUSP4 p.Ala212Ser Uncertain significance ★ ⚠ same type
DUSP4 p.Ala341Ser Uncertain significance ★ ⚠ same type
DUSP4 p.Arg213Gln Uncertain significance ★ ⚠ same type
DUSP4 p.Arg213Trp Uncertain significance ★ ⚠ same type
DUSP4 p.Arg273His Uncertain significance ★ ⚠ same type
DUSP4 p.Arg313His Uncertain significance ★ ⚠ same type

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/dusp4-p-his191 (accessed [today's date]).

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