Is CCBE1 p.Ile52= (c.156C>T) pathogenic?

CCBE1 p.Ile52= (c.156C>T) is classified Benign in CCBE1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-22). Low-frequency (popmax 1.87%, eas); Associated with Hennekam lymphangiectasia-lymphedema syndrome 1.

What condition is associated with CCBE1 p.Ile52= (c.156C>T)?

CCBE1 p.Ile52= (c.156C>T) is associated with Hennekam lymphangiectasia-lymphedema syndrome 1 (ClinVar).

How common is CCBE1 p.Ile52= (c.156C>T) in the general population?

CCBE1 p.Ile52= (c.156C>T) is low-frequency (popmax 1.87%, eas) (gnomAD).

CCBE1 p.Ile52=

c.156C>T · rs2288598 · VCV327709

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.87%, eas)

Conditions

Hennekam lymphangiectasia-lymphedema syndrome 1

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 3.3	GERP 0.83, phastCons 1
Overall
CADD	11.74	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.87% East Asian · 838/44,878 alleles

Filtering AF 1.76% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.72%

Overall 0.101% 1,634/1,614,028 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.87%	54
South Asian	0.731%	137
Remaining individualsnot grpmax-eligible	0.157%	638
Middle Eastern	0.0166%	6,042
Admixed American	0.00833%	12,004
African / African-American	0.00533%	18,765
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
European (non-Finnish)	0.00178%	56,188

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.Ile52=
Coding: c.156C>T
MANE Select: NM_133459
dbSNP: rs2288598
Type: single nucleotide variant
Location: chr18:59696685 (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

Disease context

Hennekam lymphangiectasia-lymphedema syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CCBE1 p.Ile52Thr Uncertain significance ★ ⚠ same residue
CCBE1 p.Arg108Ter Pathogenic ★★ same condition
CCBE1 c.654+5G>C Uncertain significance ★★ same condition
CCBE1 c.*203A>G Uncertain significance ★★ same condition
CCBE1 c.*4173A>G Uncertain significance ★★ same condition
CCBE1 p.Ala28Val Uncertain significance ★★ ⚠ same condition
CCBE1 p.Ala96Gly Uncertain significance ★★ ⚠ same condition
CCBE1 p.Arg125Trp 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-ile52 (accessed [today's date]).

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