Is BBS7 p.Ala217Glu (c.650C>A) pathogenic?

BBS7 p.Ala217Glu (c.650C>A) is classified Uncertain significance in BBS7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-13). AlphaMissense: likely benign (0.2482); Very rare (popmax 0.0011%, sas); Associated with Bardet-Biedl syndrome 7.

What condition is associated with BBS7 p.Ala217Glu (c.650C>A)?

BBS7 p.Ala217Glu (c.650C>A) is associated with Bardet-Biedl syndrome 7 (ClinVar).

How common is BBS7 p.Ala217Glu (c.650C>A) in the general population?

BBS7 p.Ala217Glu (c.650C>A) is very rare (popmax 0.0011%, sas) (gnomAD).

How is Bardet-Biedl syndrome inherited?

Typically Autosomal recessive, Oligogenic (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about BBS7 p.Ala217Glu (c.650C>A)?

AlphaMissense predicts likely benign (score 0.2482) — an in-silico prediction, not a clinical call.

BBS7 p.Ala217Glu

c.650C>A · VCV3589803

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2482 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Bardet-Biedl syndrome 7

Computational evidence

Protein change
AlphaMissense	0.2482	likely benign
REVEL	0.467	indeterminate
SaProt	LLR -2.18	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.83, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 44 kb · p 0.00015 · regional, not allelic
Overall
CADD	22.6	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 0.0011% South Asian · 1/90,926 alleles

Overall 6.85e-05% 1/1,460,384 alleles · very 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: BBS7
Protein: p.Ala217Glu
Coding: c.650C>A
MANE Select: NM_176824
Type: single nucleotide variant
Location: chr4:121854772 (GRCh38)
Gene constraint: LOEUF 0.701 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.99

Full BBS7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bardet-Biedl syndrome 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Bardet-Biedl syndrome (Orphanet):

Inheritance: Autosomal recessive, Oligogenic
Onset: Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

BBS7 p.Ala217Val Uncertain significance ★★ ⚠ same residue
BBS7 p.Ala217= Conflicting classifications of pathogenicity ★ same residue
BBS7 p.Ala217fs Pathogenic/Likely pathogenic ★★ same residue
BBS7 c.1371+1G>A Likely pathogenic ★★ same condition
BBS7 c.1512-1G>A Likely pathogenic ★★ same condition
BBS7 c.1677-2A>G Pathogenic/Likely pathogenic ★★ same condition
BBS7 c.1891-2A>C Pathogenic/Likely pathogenic ★★ same condition
BBS7 c.529-2A>G Pathogenic/Likely pathogenic ★★ 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/bbs7-p-ala217glu (accessed [today's date]).

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