Is BBS2 p.Ala370= (c.1110T>C) pathogenic?

BBS2 p.Ala370= (c.1110T>C) is classified Benign/Likely benign in BBS2 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-28). Low-frequency (popmax 1.29%, afr); Associated with retinitis pigmentosa 74.

What condition is associated with BBS2 p.Ala370= (c.1110T>C)?

BBS2 p.Ala370= (c.1110T>C) is associated with retinitis pigmentosa 74, Bardet-Biedl syndrome 2, Bardet-Biedl syndrome (ClinVar).

How common is BBS2 p.Ala370= (c.1110T>C) in the general population?

BBS2 p.Ala370= (c.1110T>C) is low-frequency (popmax 1.29%, afr) (gnomAD).

How is Retinitis pigmentosa inherited?

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

BBS2 p.Ala370=

c.1110T>C · rs148990271 · VCV166731

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.29%, afr)

Conditions

retinitis pigmentosa 74

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 -5.9	GERP -3.1
Overall
CADD	0.023	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.29% African / African-American · 970/75,032 alleles

Filtering AF 1.23% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2%

Overall 0.0722% 1,165/1,614,172 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.29%	77
Remaining individualsnot grpmax-eligible	0.139%	718
Admixed American	0.128%	780
Middle Eastern	0.099%	1,010
South Asian	0.00439%	22,771
European (non-Finnish)	0.00178%	56,192

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.Ala370=
Coding: c.1110T>C
MANE Select: NM_031885
dbSNP: rs148990271
Type: single nucleotide variant
Location: chr16:56501468 (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

retinitis pigmentosa 74 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bardet-Biedl syndrome 2 Bardet-Biedl syndrome

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

BBS2 p.Ala370Thr 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
BBS2 c.1397+1G>A Pathogenic/Likely pathogenic ★★ same condition
BBS2 c.1397+2T>C 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-ala370 (accessed [today's date]).

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