Is CCBE1 p.Arg162Trp (c.484C>T) pathogenic?

CCBE1 p.Arg162Trp (c.484C>T) is classified Uncertain significance in CCBE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-15). AlphaMissense: likely benign (0.1082); Ultra-rare (popmax 0.02%, afr); Associated with Inborn genetic diseases.

What condition is associated with CCBE1 p.Arg162Trp (c.484C>T)?

CCBE1 p.Arg162Trp (c.484C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CCBE1 p.Arg162Trp (c.484C>T) in the general population?

CCBE1 p.Arg162Trp (c.484C>T) is ultra-rare (popmax 0.02%, afr) (gnomAD).

What do computational predictors say about CCBE1 p.Arg162Trp (c.484C>T)?

AlphaMissense predicts likely benign (score 0.1082) — an in-silico prediction, not a clinical call.

CCBE1 p.Arg162Trp

c.484C>T · rs562613006 · VCV1349317

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1082 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1082	likely benign
REVEL	0.675	pathogenic-leaning
SaProt	LLR -10.92	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.4, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 261 kb · p 0.54 · regional, not allelic
Overall
CADD	25.0	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 0.02% African / African-American · 15/75,018 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00988%

Overall 0.00347% 56/1,613,670 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.02%	5,001
Admixed American	0.01%	10,002
Remaining individualsnot grpmax-eligible	0.0032%	31,241
European (non-Finnish)	0.00271%	36,872
South Asian	0.0011%	91,054

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.Arg162Trp
Coding: c.484C>T
MANE Select: NM_133459
dbSNP: rs562613006
Type: single nucleotide variant
Location: chr18:59466808 (GRCh38)
Gene constraint: LOEUF 0.933 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 162: a disulfide bond; the egf-like; calcium-binding domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CCBE1 p.Arg162Gln Uncertain significance ★★ ⚠ same residue
CCBE1 p.Ala28Val Uncertain significance ★★ ⚠ same condition
CCBE1 p.Ala322Val Uncertain significance ★★ ⚠ same condition
CCBE1 p.Arg121Gln Uncertain significance ★★ ⚠ same condition
CCBE1 p.Arg127Gln Uncertain significance ★★ ⚠ same condition
CCBE1 p.Arg301Trp Uncertain significance ★★ ⚠ same condition
CCBE1 p.Arg346Leu Uncertain significance ★★ ⚠ same condition
CCBE1 p.Asn347Ser Uncertain significance ★★ ⚠ same condition

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-arg162trp (accessed [today's date]).

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