Is CCAR2 p.Ala406= (c.1218C>T) pathogenic?

CCAR2 p.Ala406= (c.1218C>T) is classified Benign in CCAR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-21). Common (popmax 12.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with CCAR2-related disorder.

What condition is associated with CCAR2 p.Ala406= (c.1218C>T)?

CCAR2 p.Ala406= (c.1218C>T) is associated with CCAR2-related disorder (ClinVar).

CCAR2 p.Ala406=

Q: How common is CCAR2 p.Ala406= (c.1218C>T) in the general population?

CCAR2 p.Ala406= (c.1218C>T) is common (popmax 12.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1218C>T · rs7001453 · VCV3037246

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 12.8%, 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	0.118	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -3.8
Overall
CADD	0.419	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.8% African / African-American · 9,613/74,956 alleles

Filtering AF 12.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.5%

Overall 0.701% 11,315/1,613,378 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	12.8%	8
Admixed American	1.1%	91
Remaining individualsnot grpmax-eligible	1.03%	97
Middle Eastern	0.545%	184
South Asian	0.0296%	3,373
European (non-Finnish)	0.0287%	3,490
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,790
Finnishnot grpmax-eligible	0.00471%	21,239
East Asian	0.00223%	44,882

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.Ala406=
Coding: c.1218C>T
MANE Select: NM_001393997
dbSNP: rs7001453
Type: single nucleotide variant
Location: chr8:22615437 (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

Disease context

CCAR2-related disorder

Similar variants

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.Ala819= Benign same condition
CCAR2 p.Arg418Gln Likely benign same condition
CCAR2 p.Asp292= Likely benign same condition
CCAR2 p.Asp372= Likely benign same condition
CCAR2 p.Asp469= 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-ala406 (accessed [today's date]).

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