Is CCAR1 p.Arg353Trp (c.1057C>T) pathogenic?

CCAR1 p.Arg353Trp (c.1057C>T) is classified Uncertain significance in CCAR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-08). AlphaMissense: likely pathogenic (0.9733); Very rare (popmax 0.00659%, sas).

How common is CCAR1 p.Arg353Trp (c.1057C>T) in the general population?

CCAR1 p.Arg353Trp (c.1057C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about CCAR1 p.Arg353Trp (c.1057C>T)?

AlphaMissense predicts likely pathogenic (score 0.9733) — an in-silico prediction, not a clinical call.

CCAR1 p.Arg353Trp

c.1057C>T · rs143403057 · VCV2570488

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9733 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9733	likely pathogenic
REVEL	0.162	moderately benign-leaning
SaProt	LLR -12.26	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1.4, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 44 kb · p 4.8e-18 · regional, not allelic
Overall
CADD	26.0	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 0.00659% South Asian · 6/91,090 alleles

Filtering AF 0.00519% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00474%

Overall 0.00545% 88/1,613,878 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,182
Remaining individualsnot grpmax-eligible	0.0064%	15,620
European (non-Finnish)	0.00636%	15,732
East Asian	0.00223%	44,888
Admixed American	0.00167%	59,986
African / African-American	0.00133%	74,908

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.Arg353Trp
Coding: c.1057C>T
MANE Select: NM_018237
dbSNP: rs143403057
Type: single nucleotide variant
Location: chr10:68749624 (GRCh38)
Gene constraint: LOEUF 0.651 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.55
Residue 353: the 'interaction with gata2' region; the 'disordered' 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.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
CCAR1 p.Arg340Leu 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-arg353trp (accessed [today's date]).

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