Is CCAR2 p.Pro607= (c.1821G>A) pathogenic?

CCAR2 p.Pro607= (c.1821G>A) is classified Benign in CCAR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-21). Rare (popmax 0.961%, afr); Associated with CCAR2-related disorder.

What condition is associated with CCAR2 p.Pro607= (c.1821G>A)?

CCAR2 p.Pro607= (c.1821G>A) is associated with CCAR2-related disorder (ClinVar).

How common is CCAR2 p.Pro607= (c.1821G>A) in the general population?

CCAR2 p.Pro607= (c.1821G>A) is rare (popmax 0.961%, afr) (gnomAD).

CCAR2 p.Pro607=

c.1821G>A · rs141429680 · VCV3039673

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.961%, afr)

Conditions

CCAR2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.01	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9	GERP -3.8
Overall
CADD	0.758	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.961% African / African-American · 721/75,020 alleles

Filtering AF 0.903% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.88%

Overall 0.0516% 833/1,613,078 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.961%	104
Middle Eastern	0.0927%	1,078
Admixed American	0.08%	1,250
Remaining individualsnot grpmax-eligible	0.0657%	1,522
South Asian	0.0022%	45,529
European (non-Finnish)	0.00136%	73,750

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.Pro607=
Coding: c.1821G>A
MANE Select: NM_001393997
dbSNP: rs141429680
Type: single nucleotide variant
Location: chr8:22616224 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.61 · 1 PDB
Residue 607: the 'disordered' region

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

Disease context

CCAR2-related disorder

Similar variants

CCAR2 p.Pro607Arg Uncertain significance ★ ⚠ same residue
CCAR2 p.Pro607Leu Uncertain significance ★ ⚠ same residue
CCAR2 c.150+8C>G Benign same condition
CCAR2 c.1609-5A>G Benign same condition
CCAR2 c.2522-3C>T Likely benign same condition
CCAR2 p.Ala406= Benign same condition
CCAR2 p.Ala819= Benign same condition
CCAR2 p.Arg418Gln Likely benign same condition

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-pro607 (accessed [today's date]).

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