Is BBS12 p.Arg12del (c.31AGA[1]) pathogenic?

BBS12 p.Arg12del (c.31AGA[1]) is classified Uncertain significance in BBS12 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-07-20). Very rare (popmax 0.00161%, nfe); Associated with BBS12-related disorder.

What condition is associated with BBS12 p.Arg12del (c.31AGA[1])?

BBS12 p.Arg12del (c.31AGA[1]) is associated with BBS12-related disorder, Bardet-Biedl syndrome 12, Bardet-Biedl syndrome (ClinVar).

How common is BBS12 p.Arg12del (c.31AGA[1]) in the general population?

BBS12 p.Arg12del (c.31AGA[1]) is very rare (popmax 0.00161%, nfe) (gnomAD).

BBS12 p.Arg12del

c.31AGA[1] · rs752885483 · VCV444639

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Conditions

BBS12-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.17	GERP 0.49, phastCons 0.002
Overall
CADD	15.97	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00161% European (non-Finnish) · 19/1,180,026 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00136% 22/1,614,146 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,248
European (non-Finnish)grpmax	0.00161%	62,107
South Asian	0.0011%	91,066

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg12del
Coding: c.31AGA[1]
MANE Select: NM_152618
dbSNP: rs752885483
Type: Microsatellite
Location: chr4:122741922 (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

BBS12-related disorder

Also linked: Bardet-Biedl syndrome 12 Bardet-Biedl syndrome

Similar variants

BBS12 p.Arg12Lys Uncertain significance ★ ⚠ same residue
BBS12 p.Arg12= Likely benign ★ same residue
BBS12 p.Asn366fs Likely pathogenic ★★ same condition
BBS12 p.Asp687fs Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.His260fs Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.Pro632fs Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.Ser196_Tyr197insTer Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.Tyr640_Ser641delinsTer 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-arg12del (accessed [today's date]).

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