Is CCAR2 p.Leu783Pro (c.2348T>C) pathogenic?

CCAR2 p.Leu783Pro (c.2348T>C) is classified Uncertain significance in CCAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-17). AlphaMissense: ambiguous (0.3459); Absent from gnomAD v4.1.

How common is CCAR2 p.Leu783Pro (c.2348T>C) in the general population?

CCAR2 p.Leu783Pro (c.2348T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCAR2 p.Leu783Pro (c.2348T>C)?

AlphaMissense predicts ambiguous (score 0.3459) — an in-silico prediction, not a clinical call.

CCAR2 p.Leu783Pro

c.2348T>C · rs1316427296 · VCV2246046

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3459 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3459	ambiguous
REVEL	0.226	benign-leaning
SaProt	LLR -8.45	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.54 · regional, not allelic
Overall
CADD	23.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCAR2
Protein: p.Leu783Pro
Coding: c.2348T>C
MANE Select: NM_001393997
dbSNP: rs1316427296
Type: single nucleotide variant
Location: chr8:22618842 (GRCh38)
Gene constraint: LOEUF 0.288 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.61 · 1 PDB
Residue 783: the 'interaction with nr1d1' region

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

Similar variants

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
CCAR2 p.Ala214Ser Uncertain significance ★ ⚠ same type
CCAR2 p.Ala293Gly 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-leu783pro (accessed [today's date]).

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