Is CCBE1 p.Asp178Glu (c.534C>A) pathogenic?

CCBE1 p.Asp178Glu (c.534C>A) is classified Uncertain significance in CCBE1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-24). AlphaMissense: likely benign (0.102); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with CCBE1 p.Asp178Glu (c.534C>A)?

CCBE1 p.Asp178Glu (c.534C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CCBE1 p.Asp178Glu (c.534C>A) in the general population?

CCBE1 p.Asp178Glu (c.534C>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CCBE1 p.Asp178Glu (c.534C>A)?

AlphaMissense predicts likely benign (score 0.102) — an in-silico prediction, not a clinical call.

CCBE1 p.Asp178Glu

c.534C>A · rs146639693 · VCV1431944

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.102 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.102	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -5.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 0.098, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 261 kb · p 0.54 · regional, not allelic
Overall
CADD	14.16	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,044 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00149% 24/1,612,918 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,522
European (non-Finnish)	0.00186%	53,624

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.Asp178Glu
Coding: c.534C>A
MANE Select: NM_133459
dbSNP: rs146639693
Type: single nucleotide variant
Location: chr18:59466758 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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CCBE1 p.Arg127Gln Uncertain significance ★★ ⚠ same condition
CCBE1 p.Arg162Gln Uncertain significance ★★ ⚠ same condition
CCBE1 p.Arg162Trp Uncertain significance ★★ ⚠ same condition
CCBE1 p.Arg301Trp Uncertain significance ★★ ⚠ same condition
CCBE1 p.Arg346Leu 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-asp178glu (accessed [today's date]).

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