Is CASP2 p.His187fs (c.560_561del) pathogenic?

CASP2 p.His187fs (c.560561del) is classified Likely pathogenic in CASP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-29). Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with CASP2 p.His187fs (c.560_561del)?

CASP2 p.His187fs (c.560_561del) is associated with Inborn genetic diseases (ClinVar).

How common is CASP2 p.His187fs (c.560_561del) in the general population?

CASP2 p.His187fs (c.560_561del) is very rare (popmax 0.00167%, amr) (gnomAD).

CASP2 p.His187fs

c.560_561del · rs1801677859 · VCV985938

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.8	GERP -3

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,002 alleles

Overall 0.000137% 2/1,456,086 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,002
European (non-Finnish)	8.51e-05%	1,174,835

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: CASP2
Protein: p.His187fs
Coding: c.560_561del
MANE Select: NM_032982
dbSNP: rs1801677859
Type: Microsatellite
Location: chr7:143294310 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.95 · 17 PDB
Residue 187: a UniProt-annotated variant site (in mrt80; likely pathogenic); an α-helix

Full CASP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CASP2 c.876+1G>T Pathogenic ★ same condition
CASP2 p.Arg44Ter Pathogenic ★ same condition
CASP2 p.Gln392Ter Pathogenic ★ same condition
CASP2 p.Tyr386fs Pathogenic ★ same condition

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/casp2-p-his187fs (accessed [today's date]).

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