Is CCBE1 p.Ile349= (c.1047C>T) pathogenic?

CCBE1 p.Ile349= (c.1047C>T) is classified Likely benign in CCBE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-01). Very rare (popmax 0.00133%, afr).

How common is CCBE1 p.Ile349= (c.1047C>T) in the general population?

CCBE1 p.Ile349= (c.1047C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

CCBE1 p.Ile349=

c.1047C>T · rs779502589 · VCV1638697

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -0.53, phastCons 0.86
Overall
CADD	7.841	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,938 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,614,102 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,938
European (non-Finnish)	0.000508%	196,674

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.Ile349=
Coding: c.1047C>T
MANE Select: NM_133459
dbSNP: rs779502589
Type: single nucleotide variant
Location: chr18:59436082 (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.Ile349Val 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-ile349 (accessed [today's date]).

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