Is BBS2 p.His384= (c.1152C>T) pathogenic?

BBS2 p.His384= (c.1152C>T) is classified Likely benign in BBS2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-21). Ultra-rare (popmax 0.0227%, afr); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS2 p.His384= (c.1152C>T)?

BBS2 p.His384= (c.1152C>T) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS2 p.His384= (c.1152C>T) in the general population?

BBS2 p.His384= (c.1152C>T) is ultra-rare (popmax 0.0227%, 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.His384=

c.1152C>T · rs774493134 · VCV531841

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Conditions

Bardet-Biedl syndrome

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 0.87	GERP -0.51, phastCons 1
Overall
CADD	1.515	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0227% African / African-American · 17/74,930 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.00167% 27/1,614,066 alleles · ultra-rare exomes 20/1,461,892 · genomes 7/152,174 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,408
Admixed American	0.00833%	12,000
Remaining individualsnot grpmax-eligible	0.0064%	15,621
European (non-Finnish)	8.47e-05%	1,180,032

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.His384=
Coding: c.1152C>T
MANE Select: NM_031885
dbSNP: rs774493134
Type: single nucleotide variant
Location: chr16:56501426 (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

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.His384Asn Uncertain significance ★ ⚠ same residue
BBS2 p.His384fs Pathogenic ★ same residue
BBS2 c.118-1G>T Likely pathogenic ★★ same condition
BBS2 c.118-2A>C Likely pathogenic ★★ same condition
BBS2 c.1225+2T>C 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-his384 (accessed [today's date]).

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