Is CCAR2 p.Ser308= (c.924G>A) pathogenic?

CCAR2 p.Ser308= (c.924G>A) is classified Benign in CCAR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-17). Common (popmax 36%, sas) — too common for a highly-penetrant pathogenic allele; Associated with CCAR2-related disorder.

What condition is associated with CCAR2 p.Ser308= (c.924G>A)?

CCAR2 p.Ser308= (c.924G>A) is associated with CCAR2-related disorder (ClinVar).

CCAR2 p.Ser308=

Q: How common is CCAR2 p.Ser308= (c.924G>A) in the general population?

CCAR2 p.Ser308= (c.924G>A) is common (popmax 36%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.924G>A · rs3736147 · VCV3060085

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 36%, sas) — 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.7, phastCons 1
Overall
CADD	11.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 36% South Asian · 32,766/91,072 alleles

Filtering AF 35.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 35.5%

Overall 31.1% 502,186/1,613,598 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	36%	3
European (non-Finnish)	32.7%	3
Amishnot grpmax-eligible	31.5%	3
Ashkenazi Jewishnot grpmax-eligible	31.5%	3
Remaining individualsnot grpmax-eligible	30.5%	3
East Asian	28.9%	3
Finnishnot grpmax-eligible	25.9%	4
Middle Eastern	25%	4
Admixed American	23.1%	4
African / African-American	13.8%	7

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.Ser308=
Coding: c.924G>A
MANE Select: NM_001393997
dbSNP: rs3736147
Type: single nucleotide variant
Location: chr8:22614311 (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 p.Ser308Ala 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
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-ser308 (accessed [today's date]).

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