Is CCBE1 p.Arg118Gln (c.353G>A) pathogenic?

CCBE1 p.Arg118Gln (c.353G>A) is classified Uncertain significance in CCBE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-29). AlphaMissense: likely benign (0.1212); Very rare (popmax 0.00549%, sas).

How common is CCBE1 p.Arg118Gln (c.353G>A) in the general population?

CCBE1 p.Arg118Gln (c.353G>A) is very rare (popmax 0.00549%, sas) (gnomAD).

What do computational predictors say about CCBE1 p.Arg118Gln (c.353G>A)?

AlphaMissense predicts likely benign (score 0.1212) — an in-silico prediction, not a clinical call.

CCBE1 p.Arg118Gln

c.353G>A · VCV4778332

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1212 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1212	likely benign
REVEL	0.234	benign-leaning
SaProt	LLR -8.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.44, phastCons 0.99
Regional constraint	o/e 1.03	unconstrained · MANE · 261 kb · p 0.54 · regional, not allelic
Overall
CADD	25.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,080 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000681% 11/1,614,200 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,216
African / African-American	0.00266%	37,529
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)	0.000254%	393,345

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.Arg118Gln
Coding: c.353G>A
MANE Select: NM_133459
Type: single nucleotide variant
Location: chr18:59469520 (GRCh38)
Gene constraint: LOEUF 0.933 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61

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

Similar variants

CCBE1 p.Arg118Ter Pathogenic/Likely pathogenic ★★ same residue
CCBE1 p.Arg118= Conflicting classifications of pathogenicity ★ same residue
CCBE1 p.Arg118Leu Uncertain significance ★ ⚠ same residue
CCBE1 p.Arg108Ter 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

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-arg118gln (accessed [today's date]).

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