Is BBS12 p.Phe536= (c.1608C>T) pathogenic?

BBS12 p.Phe536= (c.1608C>T) is classified Likely benign in BBS12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). Very rare (popmax 0.00801%, afr); Associated with Bardet-Biedl syndrome.

What condition is associated with BBS12 p.Phe536= (c.1608C>T)?

BBS12 p.Phe536= (c.1608C>T) is associated with Bardet-Biedl syndrome (ClinVar).

How common is BBS12 p.Phe536= (c.1608C>T) in the general population?

BBS12 p.Phe536= (c.1608C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

BBS12 p.Phe536=

c.1608C>T · rs148277417 · VCV1144822

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00801%, 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 -0.31	GERP -3.7, phastCons 0.14
Overall
CADD	3.171	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% African / African-American · 6/74,918 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000372% 6/1,614,086 alleles · very rare

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: BBS12
Protein: p.Phe536=
Coding: c.1608C>T
MANE Select: NM_152618
dbSNP: rs148277417
Type: single nucleotide variant
Location: chr4:122743500 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.92

Full BBS12 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

BBS12 p.Phe536Leu Uncertain significance ★ ⚠ same residue
BBS12 p.Phe536Cys Uncertain significance ★ ⚠ same residue
BBS12 p.Phe536Val Uncertain significance ⚠ same residue
BBS12 p.Ala289Pro Likely pathogenic ★★ same condition
BBS12 p.Arg214Ter Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.Arg355Ter Pathogenic ★★ same condition
BBS12 p.Arg675Ter Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.Gln149Ter Pathogenic/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/bbs12-p-phe536 (accessed [today's date]).

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