Is CASP1 p.Arg240Gln (c.719G>A) pathogenic?

CASP1 p.Arg240Gln (c.719G>A) is classified Likely benign in CASP1 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2023-03-13). AlphaMissense: likely benign (0.0921); Rare (popmax 0.314%, mid); Associated with CASP1-related disorder.

What condition is associated with CASP1 p.Arg240Gln (c.719G>A)?

CASP1 p.Arg240Gln (c.719G>A) is associated with CASP1-related disorder (ClinVar).

How common is CASP1 p.Arg240Gln (c.719G>A) in the general population?

CASP1 p.Arg240Gln (c.719G>A) is rare (popmax 0.314%, mid) (gnomAD).

What do computational predictors say about CASP1 p.Arg240Gln (c.719G>A)?

AlphaMissense predicts likely benign (score 0.0921) — an in-silico prediction, not a clinical call.

CASP1 p.Arg240Gln

c.719G>A · rs45617533 · VCV3041613

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0921 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.314%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CASP1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0921	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -5.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.7
Regional constraint	o/e 0.99	unconstrained · MANE · 8,852 bp · p 0.8 · regional, not allelic
Overall
CADD	11.13	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 0.314% Middle Eastern · 19/6,060 alleles

Filtering AF 0.206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.204%

Overall 0.178% 2,876/1,613,682 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.314%	319
European (non-Finnish)	0.213%	469
Finnishnot grpmax-eligible	0.137%	728
Admixed American	0.135%	740
Remaining individualsnot grpmax-eligible	0.134%	744
Ashkenazi Jewishnot grpmax-eligible	0.0676%	1,480
South Asian	0.0505%	1,980
African / African-American	0.0267%	3,747

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: CASP1
Protein: p.Arg240Gln
Coding: c.719G>A
MANE Select: NM_001257118
dbSNP: rs45617533
Type: single nucleotide variant
Location: chr11:105029808 (GRCh38)
Gene constraint: LOEUF 0.816 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 82.48 · 42 PDB
Residue 240: a β-strand

Full CASP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CASP1-related disorder

Similar variants

CASP1 p.Arg240Trp Uncertain significance ★ ⚠ same residue
CASP1 p.Arg221Cys Likely benign ⚠ same condition
CASP1 p.Arg143= Benign ★★ same type
CASP1 p.Ile328= Likely benign ★★ same type
CASP1 p.Lys37Gln Benign ★★ same type
CASP1 p.Ala141Gly Uncertain significance ★ ⚠ same type
CASP1 p.Ala141Thr Uncertain significance ★ ⚠ same type
CASP1 p.Ala217Ser 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/casp1-p-arg240gln (accessed [today's date]).

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