Is BBS12 p.Arg55Ser (c.165G>C) pathogenic?

BBS12 p.Arg55Ser (c.165G>C) is classified Uncertain significance in BBS12 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-14). AlphaMissense: ambiguous (0.5545); Very rare (popmax 0.00458%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BBS12 p.Arg55Ser (c.165G>C)?

BBS12 p.Arg55Ser (c.165G>C) is associated with Inborn genetic diseases, Bardet-Biedl syndrome (ClinVar).

How common is BBS12 p.Arg55Ser (c.165G>C) in the general population?

BBS12 p.Arg55Ser (c.165G>C) is very rare (popmax 0.00458%, nfe) (gnomAD).

What do computational predictors say about BBS12 p.Arg55Ser (c.165G>C)?

AlphaMissense predicts ambiguous (score 0.5545) — an in-silico prediction, not a clinical call.

BBS12 p.Arg55Ser

c.165G>C · rs1160982211 · VCV2191597

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.5545 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00458%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5545	ambiguous
REVEL	0.531	indeterminate
SaProt	LLR -6.42	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -3.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 2,129 bp · p 0.0042 · regional, not allelic
Overall
CADD	20.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00458% European (non-Finnish) · 54/1,180,004 alleles

Filtering AF 0.00358% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00321%

Overall 0.00341% 55/1,613,974 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00458%	21,852
Admixed American	0.00167%	59,998

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.Arg55Ser
Coding: c.165G>C
MANE Select: NM_152618
dbSNP: rs1160982211
Type: single nucleotide variant
Location: chr4:122742057 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bardet-Biedl syndrome

Similar variants

BBS12 p.Arg55= Likely benign ★ 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
BBS12 p.Gln228Ter Pathogenic/Likely pathogenic ★★ same condition
BBS12 p.Gln300Ter 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-arg55ser (accessed [today's date]).

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