Is CASP2 p.Arg397Gln (c.1190G>A) pathogenic?

CASP2 p.Arg397Gln (c.1190G>A) is classified Uncertain significance in CASP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-14). AlphaMissense: likely benign (0.0739); Rare (popmax 0.132%, mid).

How common is CASP2 p.Arg397Gln (c.1190G>A) in the general population?

CASP2 p.Arg397Gln (c.1190G>A) is rare (popmax 0.132%, mid) (gnomAD).

What do computational predictors say about CASP2 p.Arg397Gln (c.1190G>A)?

AlphaMissense predicts likely benign (score 0.0739) — an in-silico prediction, not a clinical call.

CASP2 p.Arg397Gln

c.1190G>A · rs369524386 · VCV2596943

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0739 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.132%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0739	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -5.48	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 7.3	GERP 2.4, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 13 kb · p 0.00043 · regional, not allelic
Overall
CADD	20.9	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 0.132% Middle Eastern · 8/6,082 alleles

Filtering AF 0.0654% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0477%

Overall 0.00384% 62/1,614,054 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.132%	760
East Asian	0.00445%	22,447
European (non-Finnish)	0.00373%	26,818
Admixed American	0.00333%	30,002
Remaining individualsnot grpmax-eligible	0.0032%	31,244
South Asian	0.0022%	45,542
Finnishnot grpmax-eligible	0.00156%	64,038
African / African-American	0.00133%	74,934

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: CASP2
Protein: p.Arg397Gln
Coding: c.1190G>A
MANE Select: NM_032982
dbSNP: rs369524386
Type: single nucleotide variant
Location: chr7:143304746 (GRCh38)
Gene constraint: LOEUF 0.936 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.95 · 17 PDB
Residue 397: a UniProt-annotated variant site (in mrt80; likely pathogenic); an α-helix

Full CASP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CASP2 p.Gln331Glu Uncertain significance ★★ ⚠ same type
CASP2 p.Ala412= Likely benign ★★ same type
CASP2 p.Gly7= Likely benign ★★ same type
CASP2 p.Ile387= Benign/Likely benign ★★ same type
CASP2 p.Lys254= Benign/Likely benign ★★ same type
CASP2 p.Thr267= Benign/Likely benign ★★ same type
CASP2 p.Tyr151= Benign ★★ same type
CASP2 p.Val29= Benign ★★ 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/casp2-p-arg397gln (accessed [today's date]).

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