Is CCBE1 p.Pro279= (c.837C>T) pathogenic?

CCBE1 p.Pro279= (c.837C>T) is classified Benign in CCBE1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Low-frequency (popmax 1.95%, nfe); Associated with Hennekam lymphangiectasia-lymphedema syndrome 1.

What condition is associated with CCBE1 p.Pro279= (c.837C>T)?

CCBE1 p.Pro279= (c.837C>T) is associated with Hennekam lymphangiectasia-lymphedema syndrome 1 (ClinVar).

How common is CCBE1 p.Pro279= (c.837C>T) in the general population?

CCBE1 p.Pro279= (c.837C>T) is low-frequency (popmax 1.95%, nfe) (gnomAD).

CCBE1 p.Pro279=

c.837C>T · rs61745250 · VCV262356

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.95%, nfe)

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 -9.6	GERP -4.1
Overall
CADD	0.959	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.95% European (non-Finnish) · 23,021/1,180,004 alleles

Filtering AF 1.93% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.92%

Overall 1.59% 25,649/1,614,160 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.95%	51
Amishnot grpmax-eligible	1.54%	65
Remaining individualsnot grpmax-eligible	1.26%	80
Finnishnot grpmax-eligible	1.16%	86
Ashkenazi Jewishnot grpmax-eligible	0.736%	136
Admixed American	0.645%	155
South Asian	0.294%	340
African / African-American	0.269%	372
Middle Eastern	0.0826%	1,211
East Asian	0.00446%	22,433

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.Pro279=
Coding: c.837C>T
MANE Select: NM_133459
dbSNP: rs61745250
Type: single nucleotide variant
Location: chr18:59439755 (GRCh38)
Gene constraint: LOEUF 0.933 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 279: the collagen-like 1 domain; the 'disordered' region

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.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
CCBE1 p.Arg127Gln 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-pro279 (accessed [today's date]).

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