Is CCAR1 p.Arg384Cys (c.1150C>T) pathogenic?

CCAR1 p.Arg384Cys (c.1150C>T) is classified Uncertain significance in CCAR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-19). AlphaMissense: likely pathogenic (0.9838); Very rare (popmax 0.000339%, nfe).

How common is CCAR1 p.Arg384Cys (c.1150C>T) in the general population?

CCAR1 p.Arg384Cys (c.1150C>T) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about CCAR1 p.Arg384Cys (c.1150C>T)?

AlphaMissense predicts likely pathogenic (score 0.9838) — an in-silico prediction, not a clinical call.

CCAR1 p.Arg384Cys

c.1150C>T · VCV4220195

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9838 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9838	likely pathogenic
REVEL	0.46	indeterminate
SaProt	LLR -9.76	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.23 · evaluated, not missing
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	28.8	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 0.000339% European (non-Finnish) · 4/1,179,842 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,614 alleles · very rare

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: CCAR1
Protein: p.Arg384Cys
Coding: c.1150C>T
MANE Select: NM_018237
Type: single nucleotide variant
Location: chr10:68753883 (GRCh38)
Gene constraint: LOEUF 0.651 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.55
Residue 384: the 'interaction with gata2' region

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

Similar variants

CCAR1 p.Arg384His Uncertain significance ★ ⚠ same residue
CCAR1 c.1625+1G>A Uncertain significance ★ same type
CCAR1 p.Ala2Val 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

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-arg384cys (accessed [today's date]).

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