Is CASP3 p.Met233Val (c.697A>G) pathogenic?

CASP3 p.Met233Val (c.697A>G) is classified Uncertain significance in CASP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely benign (0.2148); Very rare (popmax 0.00223%, eas).

How common is CASP3 p.Met233Val (c.697A>G) in the general population?

CASP3 p.Met233Val (c.697A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CASP3 p.Met233Val (c.697A>G)?

AlphaMissense predicts likely benign (score 0.2148) — an in-silico prediction, not a clinical call.

CASP3 p.Met233Val

c.697A>G · rs1170037815 · VCV2542222

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2148 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2148	likely benign
REVEL	0.138	moderately benign-leaning
SaProt	LLR -10.88	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 1.9, phastCons 0.98
Regional constraint	o/e 0.79	unconstrained · MANE · 9,178 bp · p 0.0001 · regional, not allelic
Overall
CADD	21.3	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 0.00223% East Asian · 1/44,886 alleles

Overall 0.000137% 2/1,461,868 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,886
South Asian	0.0011%	91,082

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: CASP3
Protein: p.Met233Val
Coding: c.697A>G
MANE Select: NM_004346
dbSNP: rs1170037815
Type: single nucleotide variant
Location: chr4:184629409 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 86.64 · 135 PDB
Residue 233: an α-helix

Full CASP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CASP3 c.*337T>C Benign ★★ same type
CASP3 p.Ala254Thr Uncertain significance ★ ⚠ same type
CASP3 p.Arg164Cys Uncertain significance ★ ⚠ same type
CASP3 p.Arg79Ser Uncertain significance ★ ⚠ same type
CASP3 p.Cys148Arg Uncertain significance ★ ⚠ same type
CASP3 p.Gln225Arg Uncertain significance ★ ⚠ same type
CASP3 p.Glu98Gln Uncertain significance ★ ⚠ same type
CASP3 p.Ile126Thr 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/casp3-p-met233val (accessed [today's date]).

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