Is CCAR2 p.Glu577Ala (c.1730A>C) pathogenic?

CCAR2 p.Glu577Ala (c.1730A>C) is classified Likely benign in CCAR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-08). AlphaMissense: likely benign (0.068); Rare (popmax 0.391%, afr); Associated with CCAR2-related disorder.

What condition is associated with CCAR2 p.Glu577Ala (c.1730A>C)?

CCAR2 p.Glu577Ala (c.1730A>C) is associated with CCAR2-related disorder (ClinVar).

How common is CCAR2 p.Glu577Ala (c.1730A>C) in the general population?

CCAR2 p.Glu577Ala (c.1730A>C) is rare (popmax 0.391%, afr) (gnomAD).

What do computational predictors say about CCAR2 p.Glu577Ala (c.1730A>C)?

AlphaMissense predicts likely benign (score 0.068) — an in-silico prediction, not a clinical call.

CCAR2 p.Glu577Ala

c.1730A>C · rs143150726 · VCV3041953

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.068 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.391%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CCAR2-related disorder

Computational evidence

Protein change
AlphaMissense	0.068	likely benign
REVEL	0.278	benign-leaning
SaProt	LLR -9.40	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.9	GERP 0.87, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.54 · regional, not allelic
Overall
CADD	19.13	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.391% African / African-American · 293/74,970 alleles

Filtering AF 0.354% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.34%

Overall 0.0514% 830/1,613,786 alleles · rare exomes 581/1,461,620 · genomes 249/152,166 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.391%	256
South Asian	0.233%	430
Admixed American	0.137%	732
Middle Eastern	0.116%	865
Remaining individualsnot grpmax-eligible	0.0768%	1,302
East Asian	0.0357%	2,804
European (non-Finnish)	0.0144%	6,941
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Finnishnot grpmax-eligible	0.00156%	63,906

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.Glu577Ala
Coding: c.1730A>C
MANE Select: NM_001393997
dbSNP: rs143150726
Type: single nucleotide variant
Location: chr8:22616133 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.61 · 1 PDB
Residue 577: 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 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
CCAR2 p.Asp372= 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-glu577ala (accessed [today's date]).

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