Is CCAR2 p.Pro268Thr (c.802C>A) pathogenic?

CCAR2 p.Pro268Thr (c.802C>A) is classified Uncertain significance in CCAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: ambiguous (0.5002); Ultra-rare (popmax 0.0245%, nfe).

How common is CCAR2 p.Pro268Thr (c.802C>A) in the general population?

CCAR2 p.Pro268Thr (c.802C>A) is ultra-rare (popmax 0.0245%, nfe) (gnomAD).

What do computational predictors say about CCAR2 p.Pro268Thr (c.802C>A)?

AlphaMissense predicts ambiguous (score 0.5002) — an in-silico prediction, not a clinical call.

CCAR2 p.Pro268Thr

c.802C>A · rs147153683 · VCV2362084

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5002 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0245%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5002	ambiguous
REVEL	0.458	indeterminate
SaProt	LLR -11.43	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.54 · regional, not allelic
Overall
CADD	26.1	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 0.0245% European (non-Finnish) · 289/1,180,046 alleles

Filtering AF 0.0221% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0212%

Overall 0.0195% 315/1,613,980 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0384%	2,603
European (non-Finnish)grpmax	0.0245%	4,083
African / African-American	0.00267%	37,460

Remaining individuals 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: CCAR2
Protein: p.Pro268Thr
Coding: c.802C>A
MANE Select: NM_001393997
dbSNP: rs147153683
Type: single nucleotide variant
Location: chr8:22614189 (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-pro268thr (accessed [today's date]).

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