Is BBS2 p.Phe472= (c.1416T>C) pathogenic?

BBS2 p.Phe472= (c.1416T>C) is classified Likely benign in BBS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-07). Very rare (popmax 0.0022%, sas); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS2 p.Phe472= (c.1416T>C)?

BBS2 p.Phe472= (c.1416T>C) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS2 p.Phe472= (c.1416T>C) in the general population?

BBS2 p.Phe472= (c.1416T>C) is very rare (popmax 0.0022%, 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.Phe472=

c.1416T>C · rs971361314 · VCV2766727

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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 0.53	GERP 0.66, phastCons 0.79
Overall
CADD	6.602	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,080 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000186% 3/1,614,146 alleles · very rare exomes 3/1,461,814 · genomes 0/152,332 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,540
European (non-Finnish)	8.47e-05%	1,180,004

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.Phe472=
Coding: c.1416T>C
MANE Select: NM_031885
dbSNP: rs971361314
Type: single nucleotide variant
Location: chr16:56499889 (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 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
BBS2 c.1527+1G>A Likely pathogenic ★★ same condition
BBS2 c.345+1G>A 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-phe472 (accessed [today's date]).

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