Is BBS2 p.Pro378= (c.1134A>G) pathogenic?

BBS2 p.Pro378= (c.1134A>G) is classified Benign/Likely benign in BBS2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-01). Rare (popmax 0.7%, sas); Associated with Bardet-Biedl syndrome 2.

What condition is associated with BBS2 p.Pro378= (c.1134A>G)?

BBS2 p.Pro378= (c.1134A>G) is associated with Bardet-Biedl syndrome 2, Bardet-Biedl syndrome (ClinVar).

How common is BBS2 p.Pro378= (c.1134A>G) in the general population?

BBS2 p.Pro378= (c.1134A>G) is rare (popmax 0.7%, sas) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS2 p.Pro378=

c.1134A>G · rs185178790 · VCV319858

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.7%, sas)

Conditions

Bardet-Biedl syndrome 2

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 -3.1	GERP -3.1
Overall
CADD	5.443	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.7% South Asian · 638/91,080 alleles

Filtering AF 0.655% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.638%

Overall 0.0421% 680/1,614,146 alleles · rare exomes 639/1,461,890 · genomes 41/152,256 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.7%	143
Remaining individualsnot grpmax-eligible	0.0528%	1,894
Middle Eastern	0.0165%	6,062
East Asian	0.0111%	8,976
African / African-American	0.00133%	75,024
European (non-Finnish)	0.000169%	590,012

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: BBS2
Protein: p.Pro378=
Coding: c.1134A>G
MANE Select: NM_031885
dbSNP: rs185178790
Type: single nucleotide variant
Location: chr16:56501444 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49

Full BBS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bardet-Biedl syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bardet-Biedl syndrome

For Bardet-Biedl syndrome (Orphanet):

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

Similar variants

BBS2 c.118-1G>T Likely pathogenic ★★ same condition
BBS2 c.118-2A>C Likely pathogenic ★★ same condition
BBS2 c.118-2A>G Likely pathogenic ★★ same condition
BBS2 c.1225+2T>C Likely pathogenic ★★ same condition
BBS2 c.1225+2T>G Likely pathogenic ★★ same condition
BBS2 c.1397+1G>A Pathogenic/Likely pathogenic ★★ same condition
BBS2 c.1397+2T>C Likely pathogenic ★★ same condition
BBS2 c.1398-2A>G 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/bbs2-p-pro378 (accessed [today's date]).

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