Is BBS2 p.Lys39= (c.117G>A) pathogenic?

BBS2 p.Lys39= (c.117G>A) is classified Conflicting classifications of pathogenicity in BBS2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-01-10). Very rare (popmax 0.00133%, afr); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS2 p.Lys39= (c.117G>A)?

BBS2 p.Lys39= (c.117G>A) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 2, retinitis pigmentosa 74 (ClinVar).

How common is BBS2 p.Lys39= (c.117G>A) in the general population?

BBS2 p.Lys39= (c.117G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS2 p.Lys39=

c.117G>A · rs755877218 · VCV1021318

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Bardet-Biedl syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.69	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.70	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,024 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000479% 7/1,460,176 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,024
South Asian	0.0011%	91,042
European (non-Finnish)	0.000424%	235,801

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.Lys39=
Coding: c.117G>A
MANE Select: NM_031885
dbSNP: rs755877218
Type: single nucleotide variant
Location: chr16:56519746 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bardet-Biedl syndrome 2 retinitis pigmentosa 74

For Bardet-Biedl syndrome (Orphanet):

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

Similar variants

BBS2 p.Lys39Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
BBS2 p.Lys39Asn Likely benign same residue
BBS2 p.Lys39Gln Uncertain significance ★ ⚠ same residue
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

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-lys39 (accessed [today's date]).

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