Is CCAR2 p.Ser397Arg (c.1191C>G) pathogenic?

CCAR2 p.Ser397Arg (c.1191C>G) is classified Uncertain significance in CCAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-25). AlphaMissense: ambiguous (0.4917); Absent from gnomAD v4.1.

How common is CCAR2 p.Ser397Arg (c.1191C>G) in the general population?

CCAR2 p.Ser397Arg (c.1191C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCAR2 p.Ser397Arg (c.1191C>G)?

AlphaMissense predicts ambiguous (score 0.4917) — an in-silico prediction, not a clinical call.

CCAR2 p.Ser397Arg

c.1191C>G · VCV3828030

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4917 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4917	ambiguous
REVEL	0.405	indeterminate
SaProt	LLR -8.38	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.39	GERP -3.8, phastCons 0.07
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.54 · regional, not allelic
Overall
CADD	15.05	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCAR2
Protein: p.Ser397Arg
Coding: c.1191C>G
MANE Select: NM_001393997
Type: single nucleotide variant
Location: chr8:22614987 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.61 · 1 PDB

Full CCAR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCAR2 p.Ala388= Benign ★★ same type
CCAR2 p.Ala794= Benign ★★ same type
CCAR2 p.Arg336= Likely benign ★★ same type
CCAR2 c.1990+1G>T Uncertain significance ★ same type
CCAR2 c.2521+1G>A Uncertain significance ★ same type
CCAR2 c.927+38G>C Uncertain significance ★ same type
CCAR2 p.Ala214Ser Uncertain significance ★ ⚠ same type
CCAR2 p.Ala293Gly 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/ccar2-p-ser397arg (accessed [today's date]).

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