Is BBS12 p.Val400= (c.1200G>A) pathogenic?

BBS12 p.Val400= (c.1200G>A) is classified Benign in BBS12 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 27.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Bardet-Biedl syndrome.

What condition is associated with BBS12 p.Val400= (c.1200G>A)?

BBS12 p.Val400= (c.1200G>A) is associated with Bardet-Biedl syndrome, Bardet-Biedl syndrome 12 (ClinVar).

How is Bardet-Biedl syndrome inherited?

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

BBS12 p.Val400=

Q: How common is BBS12 p.Val400= (c.1200G>A) in the general population?

BBS12 p.Val400= (c.1200G>A) is common (popmax 27.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1200G>A · rs309371 · VCV262669

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 27.8%, afr) — too common for a highly-penetrant pathogenic allele

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 -2	GERP -3.7
Overall
CADD	0.015	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 27.8% African / African-American · 20,836/75,008 alleles

Filtering AF 27.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 27.3%

Overall 3.11% 50,143/1,614,144 alleles · common exomes 36,363/1,461,836 · genomes 13,780/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	27.8%	4
Ashkenazi Jewishnot grpmax-eligible	4.87%	21
Remaining individualsnot grpmax-eligible	3.93%	25
Admixed American	3.28%	30
Middle Eastern	3.04%	33
European (non-Finnish)	1.93%	52
Finnishnot grpmax-eligible	0.525%	191
South Asian	0.177%	566
East Asian	0.00223%	44,890

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.Val400=
Coding: c.1200G>A
MANE Select: NM_152618
dbSNP: rs309371
Type: single nucleotide variant
Location: chr4:122743092 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.92
Residue 400: a UniProt-annotated variant site (in bbs12)

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

Also linked: Bardet-Biedl syndrome 12

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.Val400Met 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
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-val400 (accessed [today's date]).

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