Is CCBE1 p.Arg282Trp (c.844C>T) pathogenic?

CCBE1 p.Arg282Trp (c.844C>T) is classified Uncertain significance in CCBE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-16). AlphaMissense: ambiguous (0.3691); Very rare (popmax 0.00666%, amr).

How common is CCBE1 p.Arg282Trp (c.844C>T) in the general population?

CCBE1 p.Arg282Trp (c.844C>T) is very rare (popmax 0.00666%, amr) (gnomAD).

What do computational predictors say about CCBE1 p.Arg282Trp (c.844C>T)?

AlphaMissense predicts ambiguous (score 0.3691) — an in-silico prediction, not a clinical call.

CCBE1 p.Arg282Trp

c.844C>T · rs550643166 · VCV2047078

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3691 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3691	ambiguous
REVEL	0.777	moderately pathogenic-leaning
SaProt	LLR -11.43	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.2	GERP 1.1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 261 kb · p 0.54 · regional, not allelic
Overall
CADD	26.1	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

Grpmax group 0.00666% Admixed American · 4/60,026 alleles

Filtering AF 0.00225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00149% 24/1,614,220 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00666%	15,006
East Asian	0.00223%	44,870
Remaining individualsnot grpmax-eligible	0.0016%	62,508
Finnishnot grpmax-eligible	0.00156%	64,046
European (non-Finnish)	0.00136%	73,752
South Asian	0.0011%	91,086

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: CCBE1
Protein: p.Arg282Trp
Coding: c.844C>T
MANE Select: NM_133459
dbSNP: rs550643166
Type: single nucleotide variant
Location: chr18:59439748 (GRCh38)
Gene constraint: LOEUF 0.933 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 282: the collagen-like 1 domain; the 'disordered' region

Full CCBE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCBE1 p.Arg282Gln Uncertain significance ★★ ⚠ same residue
CCBE1 p.Arg108Ter Pathogenic ★★ same type
CCBE1 p.Arg118Ter Pathogenic/Likely pathogenic ★★ same type
CCBE1 c.654+5G>C Uncertain significance ★★ same type
CCBE1 c.*203A>G Uncertain significance ★★ same type
CCBE1 c.*4173A>G Uncertain significance ★★ same type
CCBE1 p.Ala28Val Uncertain significance ★★ ⚠ same type
CCBE1 p.Ala322Val 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/ccbe1-p-arg282trp (accessed [today's date]).

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