Is CCAR2 p.Thr338= (c.1014G>A) pathogenic?

CCAR2 p.Thr338= (c.1014G>A) is classified Likely benign in CCAR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-20). Very rare (popmax 0.00267%, afr); Associated with CCAR2-related disorder.

What condition is associated with CCAR2 p.Thr338= (c.1014G>A)?

CCAR2 p.Thr338= (c.1014G>A) is associated with CCAR2-related disorder (ClinVar).

How common is CCAR2 p.Thr338= (c.1014G>A) in the general population?

CCAR2 p.Thr338= (c.1014G>A) is very rare (popmax 0.00267%, afr) (gnomAD).

CCAR2 p.Thr338=

c.1014G>A · rs752938636 · VCV3041917

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

CCAR2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.089	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.8	GERP -3.8
Overall
CADD	0.478	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,934 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000434% 7/1,614,000 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,467
Finnishnot grpmax-eligible	0.00156%	63,960
South Asian	0.0011%	91,086
European (non-Finnish)	0.000254%	393,343

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.Thr338=
Coding: c.1014G>A
MANE Select: NM_001393997
dbSNP: rs752938636
Type: single nucleotide variant
Location: chr8:22614476 (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.Thr338Met 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-thr338 (accessed [today's date]).

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