Is CCBE1 p.Ser7Arg (c.21C>A) pathogenic?

CCBE1 p.Ser7Arg (c.21C>A) is classified Uncertain significance in CCBE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-07). AlphaMissense: likely benign (0.1244); Ultra-rare (popmax 0.0122%, eas); Associated with Inborn genetic diseases.

What condition is associated with CCBE1 p.Ser7Arg (c.21C>A)?

CCBE1 p.Ser7Arg (c.21C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CCBE1 p.Ser7Arg (c.21C>A) in the general population?

CCBE1 p.Ser7Arg (c.21C>A) is ultra-rare (popmax 0.0122%, eas) (gnomAD).

What do computational predictors say about CCBE1 p.Ser7Arg (c.21C>A)?

AlphaMissense predicts likely benign (score 0.1244) — an in-silico prediction, not a clinical call.

CCBE1 p.Ser7Arg

c.21C>A · rs1376797071 · VCV2481474

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1244 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1244	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -5.22	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 4.1	GERP -3.2, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 261 kb · p 0.54 · regional, not allelic
Overall
CADD	20.7	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 0.0122% East Asian · 5/40,952 alleles

Filtering AF 0.00478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00308%

Overall 0.000323% 5/1,548,336 alleles · ultra-rare

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.Ser7Arg
Coding: c.21C>A
MANE Select: NM_133459
dbSNP: rs1376797071
Type: single nucleotide variant
Location: chr18:59697322 (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

CCBE1 p.Ala28Val Uncertain significance ★★ ⚠ same condition
CCBE1 p.Ala322Val Uncertain significance ★★ ⚠ same condition
CCBE1 p.Arg121Gln Uncertain significance ★★ ⚠ same condition
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-ser7arg (accessed [today's date]).

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