Is CASP1 p.Ser160Arg (c.480C>A) pathogenic?

CASP1 p.Ser160Arg (c.480C>A) is classified Uncertain significance in CASP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-24). AlphaMissense: likely benign (0.1882); Very rare (popmax 0.0022%, nfe).

How common is CASP1 p.Ser160Arg (c.480C>A) in the general population?

CASP1 p.Ser160Arg (c.480C>A) is very rare (popmax 0.0022%, nfe) (gnomAD).

What do computational predictors say about CASP1 p.Ser160Arg (c.480C>A)?

AlphaMissense predicts likely benign (score 0.1882) — an in-silico prediction, not a clinical call.

CASP1 p.Ser160Arg

c.480C>A · VCV4648441

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1882 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1882	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -5.50	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 -0.2
Regional constraint	o/e 0.99	unconstrained · MANE · 8,852 bp · p 0.8 · regional, not allelic
Overall
CADD	0.114	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% European (non-Finnish) · 26/1,179,348 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00167% 27/1,612,766 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0022%	45,359
Remaining individualsnot grpmax-eligible	0.0016%	62,422

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.Ser160Arg
Coding: c.480C>A
MANE Select: NM_001257118
Type: single nucleotide variant
Location: chr11:105030477 (GRCh38)
Gene constraint: LOEUF 0.816 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 82.48 · 42 PDB
Residue 160: a turn

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

Similar variants

CASP1 p.Ser160Asn Uncertain significance ★ ⚠ same residue
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

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-ser160arg (accessed [today's date]).

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