Is CASP3 p.Arg79Ser (c.237A>T) pathogenic?

CASP3 p.Arg79Ser (c.237A>T) is classified Uncertain significance in CASP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-16). AlphaMissense: likely benign (0.2068); Very rare (popmax 8.48e-05%, nfe).

How common is CASP3 p.Arg79Ser (c.237A>T) in the general population?

CASP3 p.Arg79Ser (c.237A>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CASP3 p.Arg79Ser (c.237A>T)?

AlphaMissense predicts likely benign (score 0.2068) — an in-silico prediction, not a clinical call.

CASP3 p.Arg79Ser

c.237A>T · rs757872342 · VCV3137596

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2068 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2068	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -5.34	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 -2.4	GERP -3.7
Regional constraint	o/e 0.79	unconstrained · MANE · 9,178 bp · p 0.0001 · regional, not allelic
Overall
CADD	7.631	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 8.48e-05% European (non-Finnish) · 1/1,179,784 alleles

Overall 0.00161% 26/1,613,690 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0777%	1,287
Remaining individualsnot grpmax-eligible	0.0032%	31,230
European (non-Finnish)grpmax	8.48e-05%	1,179,784

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg79Ser
Coding: c.237A>T
MANE Select: NM_004346
dbSNP: rs757872342
Type: single nucleotide variant
Location: chr4:184632338 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 86.64 · 135 PDB
Residue 79: 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.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
CASP3 p.Ile48Val 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-arg79ser (accessed [today's date]).

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