Is CCBE1 p.Lys172= (c.516G>A) pathogenic?

CCBE1 p.Lys172= (c.516G>A) is classified Likely benign in CCBE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-29). Absent from gnomAD v4.1.

How common is CCBE1 p.Lys172= (c.516G>A) in the general population?

CCBE1 p.Lys172= (c.516G>A) is absent from gnomAD v4.1 (gnomAD).

CCBE1 p.Lys172=

c.516G>A · VCV3663889

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.4	GERP -0.62, phastCons 0.028
Overall
CADD	7.176	PHRED · no single calibrated threshold — expert panels disagree

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.Lys172=
Coding: c.516G>A
MANE Select: NM_133459
Type: single nucleotide variant
Location: chr18:59466776 (GRCh38)
Gene constraint: LOEUF 0.933 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 172: a disulfide bond; the egf-like; calcium-binding domain

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

Similar variants

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
CCBE1 p.Ala96Gly 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-lys172 (accessed [today's date]).

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