Is CCAR2 p.Asp469= (c.1407T>C) pathogenic?

CCAR2 p.Asp469= (c.1407T>C) is classified Benign in CCAR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-06). Common (popmax 33.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with CCAR2-related disorder.

What condition is associated with CCAR2 p.Asp469= (c.1407T>C)?

CCAR2 p.Asp469= (c.1407T>C) is associated with CCAR2-related disorder (ClinVar).

CCAR2 p.Asp469=

Q: How common is CCAR2 p.Asp469= (c.1407T>C) in the general population?

CCAR2 p.Asp469= (c.1407T>C) is common (popmax 33.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1407T>C · rs6558165 · VCV3059635

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 33.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

CCAR2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.005	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.3	GERP -3.8
Overall
CADD	0.017	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 33.9% African / African-American · 25,414/74,928 alleles

Filtering AF 33.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 33.4%

Overall 5.09% 82,176/1,613,606 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	33.9%	3
Middle Eastern	9.17%	11
South Asian	7.64%	13
Remaining individualsnot grpmax-eligible	5.91%	17
Finnishnot grpmax-eligible	5.72%	17
Admixed American	4.22%	24
Ashkenazi Jewishnot grpmax-eligible	3.23%	31
European (non-Finnish)	3.21%	31
East Asian	1.33%	75
Amishnot grpmax-eligible	0.439%	228

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.Asp469=
Coding: c.1407T>C
MANE Select: NM_001393997
dbSNP: rs6558165
Type: single nucleotide variant
Location: chr8:22615711 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.61 · 1 PDB
Residue 469: 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.Asp469Tyr Benign ★ ⚠ 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
CCAR2 p.Asp292= 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-asp469 (accessed [today's date]).

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