Is CASP1 p.Met211Val (c.631A>G) pathogenic?

CASP1 p.Met211Val (c.631A>G) is classified Uncertain significance in CASP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-16). AlphaMissense: ambiguous (0.421); Very rare (popmax 0.0011%, sas).

How common is CASP1 p.Met211Val (c.631A>G) in the general population?

CASP1 p.Met211Val (c.631A>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CASP1 p.Met211Val (c.631A>G)?

AlphaMissense predicts ambiguous (score 0.421) — an in-silico prediction, not a clinical call.

CASP1 p.Met211Val

c.631A>G · VCV3995581

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.421 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
AlphaMissense	0.421	ambiguous
REVEL	0.382	indeterminate
SaProt	LLR -11.44	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 8,852 bp · p 0.8 · regional, not allelic
Overall
CADD	23.7	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 0.0011% South Asian · 1/91,014 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000373% 6/1,609,576 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,014
European (non-Finnish)	0.000425%	235,207

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.Met211Val
Coding: c.631A>G
MANE Select: NM_001257118
Type: single nucleotide variant
Location: chr11:105029896 (GRCh38)
Gene constraint: LOEUF 0.816 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 82.48 · 42 PDB
Residue 211: an α-helix

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

Similar variants

CASP1 p.Met211Ile Uncertain significance ★ ⚠ same residue
CASP1 p.Met211Thr 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

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-met211val (accessed [today's date]).

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