Is CASP1 p.Asp80Glu (c.240C>G) pathogenic?

CASP1 p.Asp80Glu (c.240C>G) is classified Uncertain significance in CASP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-25). AlphaMissense: likely pathogenic (0.6548); Very rare (popmax 0.005%, amr).

How common is CASP1 p.Asp80Glu (c.240C>G) in the general population?

CASP1 p.Asp80Glu (c.240C>G) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about CASP1 p.Asp80Glu (c.240C>G)?

AlphaMissense predicts likely pathogenic (score 0.6548) — an in-silico prediction, not a clinical call.

CASP1 p.Asp80Glu

c.240C>G · VCV3485179

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6548 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6548	likely pathogenic
REVEL	0.115	moderately benign-leaning
SaProt	LLR -11.28	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.42
Regional constraint	o/e 0.99	unconstrained · MANE · 8,852 bp · p 0.8 · regional, not allelic
Overall
CADD	13.9	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 0.005% Admixed American · 3/59,982 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000434% 7/1,613,992 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,994
European (non-Finnish)	0.000339%	294,997

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.Asp80Glu
Coding: c.240C>G
MANE Select: NM_001257118
Type: single nucleotide variant
Location: chr11:105034242 (GRCh38)
Gene constraint: LOEUF 0.816 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 82.48 · 42 PDB
Residue 80: the card domain

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

Similar variants

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
CASP1 p.Ala84Ser Uncertain significance ★ ⚠ same type
CASP1 p.Arg15Cys 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-asp80glu (accessed [today's date]).

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