Is CCAR1 p.Ala2Val (c.5C>T) pathogenic?

CCAR1 p.Ala2Val (c.5C>T) is classified Uncertain significance in CCAR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-21). AlphaMissense: likely pathogenic (0.9508); Absent from gnomAD v4.1.

How common is CCAR1 p.Ala2Val (c.5C>T) in the general population?

CCAR1 p.Ala2Val (c.5C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCAR1 p.Ala2Val (c.5C>T)?

AlphaMissense predicts likely pathogenic (score 0.9508) — an in-silico prediction, not a clinical call.

CCAR1 p.Ala2Val

c.5C>T · VCV3485822

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9508 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9508	likely pathogenic
REVEL	0.311	indeterminate
SaProt	LLR -10.10	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 44 kb · p 4.8e-18 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: CCAR1
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_018237
Type: single nucleotide variant
Location: chr10:68722509 (GRCh38)
Gene constraint: LOEUF 0.651 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.55
Residue 2: the 'interaction with ar' region

Full CCAR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCAR1 c.1625+1G>A Uncertain significance ★ same type
CCAR1 p.Ala499Asp Uncertain significance ★ ⚠ same type
CCAR1 p.Ala878Ser Uncertain significance ★ ⚠ same type
CCAR1 p.Arg300Gln Uncertain significance ★ ⚠ same type
CCAR1 p.Arg307Thr Uncertain significance ★ ⚠ same type
CCAR1 p.Arg327His Uncertain significance ★ ⚠ same type
CCAR1 p.Arg340Leu Uncertain significance ★ ⚠ same type
CCAR1 p.Arg345Gln 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/ccar1-p-ala2val (accessed [today's date]).

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