Is CBARP p.Ser223Arg (c.669C>A) pathogenic?

CBARP p.Ser223Arg (c.669C>A) is classified Uncertain significance in CBARP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-20). AlphaMissense: likely pathogenic (0.9076); Absent from gnomAD v4.1.

How common is CBARP p.Ser223Arg (c.669C>A) in the general population?

CBARP p.Ser223Arg (c.669C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CBARP p.Ser223Arg (c.669C>A)?

AlphaMissense predicts likely pathogenic (score 0.9076) — an in-silico prediction, not a clinical call.

CBARP p.Ser223Arg

c.669C>A · rs2512973773 · VCV2399659

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9076 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,451,400)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9076	likely pathogenic · top 10% in CBARP
REVEL	0.252	benign-leaning
SaProt	LLR -6.79	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.47 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 0.86, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 6,918 bp · p 1.2e-07 · regional, not allelic
Overall
CADD	29.0	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

No allele count reported in gnomAD v4.1 (AN 1,451,400). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CBARP
Protein: p.Ser223Arg
Coding: c.669C>A
MANE Select: NM_001393918
dbSNP: rs2512973773
Type: single nucleotide variant
Location: chr19:1234290 (GRCh38)
Gene constraint: LOEUF 1.107 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.23
Residue 223: the 'disordered' region

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

Similar variants

CBARP p.Arg535= Likely benign ★★ same type
CBARP c.1154+114C>G Uncertain significance ★ same type
CBARP c.1154+126G>T Uncertain significance ★ same type
CBARP c.1154+36C>G Uncertain significance ★ same type
CBARP c.1154+45C>T Uncertain significance ★ same type
CBARP c.1154+80G>A Uncertain significance ★ same type
CBARP c.1154+87C>T Uncertain significance ★ same type
CBARP p.Ala19Val 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/cbarp-p-ser223arg (accessed [today's date]).

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