Is CCBE1 p.Cys102Ser (c.305G>C) pathogenic?

CCBE1 p.Cys102Ser (c.305G>C) is classified Pathogenic in CCBE1 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2009-12-01). AlphaMissense: likely pathogenic (0.9988); Absent from gnomAD v4.1; Associated with Hennekam lymphangiectasia-lymphedema syndrome 1.

What condition is associated with CCBE1 p.Cys102Ser (c.305G>C)?

CCBE1 p.Cys102Ser (c.305G>C) is associated with Hennekam lymphangiectasia-lymphedema syndrome 1 (ClinVar).

How common is CCBE1 p.Cys102Ser (c.305G>C) in the general population?

CCBE1 p.Cys102Ser (c.305G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCBE1 p.Cys102Ser (c.305G>C)?

AlphaMissense predicts likely pathogenic (score 0.9988) — an in-silico prediction, not a clinical call.

CCBE1 p.Cys102Ser

c.305G>C · rs121908251 · VCV446

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9988 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Hennekam lymphangiectasia-lymphedema syndrome 1

Computational evidence

Protein change
AlphaMissense	0.9988	likely pathogenic ✓ concordant with ClinVar · top 1% in CCBE1
REVEL	0.926	moderately pathogenic-leaning
SaProt	LLR -15.56	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.5, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 261 kb · p 0.54 · regional, not allelic
Overall
CADD	26.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CCBE1
Protein: p.Cys102Ser
Coding: c.305G>C
MANE Select: NM_133459
dbSNP: rs121908251
Type: single nucleotide variant
Location: chr18:59469568 (GRCh38)
Gene constraint: LOEUF 0.933 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 102: a UniProt-annotated variant site (in hklls1)

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-cys102ser (accessed [today's date]).

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