Is CCAR2 p.Pro607Leu (c.1820C>T) pathogenic?

CCAR2 p.Pro607Leu (c.1820C>T) is classified Uncertain significance in CCAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-25). AlphaMissense: likely benign (0.0582); Rare (popmax 0.129%, mid).

How common is CCAR2 p.Pro607Leu (c.1820C>T) in the general population?

CCAR2 p.Pro607Leu (c.1820C>T) is rare (popmax 0.129%, mid) (gnomAD).

What do computational predictors say about CCAR2 p.Pro607Leu (c.1820C>T)?

AlphaMissense predicts likely benign (score 0.0582) — an in-silico prediction, not a clinical call.

CCAR2 p.Pro607Leu

c.1820C>T · rs142397736 · VCV3138191

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0582 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.129%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0582	likely benign
REVEL	0.371	indeterminate
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP -0.25, phastCons 0.74
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.54 · regional, not allelic
Overall
CADD	15.71	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.129% Middle Eastern · 7/5,418 alleles

Filtering AF 0.0605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0429%

Overall 0.00868% 140/1,613,014 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.129%	774
South Asian	0.0209%	4,793
Remaining individualsnot grpmax-eligible	0.0112%	8,917
European (non-Finnish)	0.00864%	11,569
African / African-American	0.004%	24,991
East Asian	0.00223%	44,862
Admixed American	0.00167%	60,010

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.Pro607Leu
Coding: c.1820C>T
MANE Select: NM_001393997
dbSNP: rs142397736
Type: single nucleotide variant
Location: chr8:22616223 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.61 · 1 PDB
Residue 607: the 'disordered' region

Full CCAR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCAR2 p.Pro607Arg Uncertain significance ★ ⚠ same residue
CCAR2 p.Pro607= Benign same residue
CCAR2 p.Ala388= Benign ★★ same type
CCAR2 p.Ala794= Benign ★★ same type
CCAR2 p.Arg336= Likely benign ★★ same type
CCAR2 c.1990+1G>T Uncertain significance ★ same type
CCAR2 c.2521+1G>A Uncertain significance ★ same type
CCAR2 c.927+38G>C Uncertain significance ★ same type

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-pro607leu (accessed [today's date]).

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