Is BBS2 p.Asn663Ter (c.1986dup) pathogenic?

BBS2 p.Asn663Ter (c.1986dup) is classified Pathogenic/Likely pathogenic in BBS2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-03-09). Very rare (popmax 0.00136%, nfe); Associated with BBS2-related disorder.

What condition is associated with BBS2 p.Asn663Ter (c.1986dup)?

BBS2 p.Asn663Ter (c.1986dup) is associated with BBS2-related disorder, Bardet-Biedl syndrome 2, retinitis pigmentosa 74 (ClinVar).

How common is BBS2 p.Asn663Ter (c.1986dup) in the general population?

BBS2 p.Asn663Ter (c.1986dup) is very rare (popmax 0.00136%, nfe) (gnomAD).

BBS2 p.Asn663Ter

c.1986dup · rs1597001788 · VCV943913

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Conditions

BBS2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 16 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP 1.8, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00136% European (non-Finnish) · 16/1,179,994 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00105% 17/1,614,056 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)grpmax	0.00136%	73,750

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: BBS2
Protein: p.Asn663Ter
Coding: c.1986dup
MANE Select: NM_031885
dbSNP: rs1597001788
Type: Duplication
Location: chr16:56485662 (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

Also linked: Bardet-Biedl syndrome 2 retinitis pigmentosa 74 Bardet-Biedl syndrome

Similar variants

BBS2 p.Asn663= Likely benign ★ same residue
BBS2 p.Ala136fs Likely pathogenic ★★ same condition
BBS2 p.Ala615fs Pathogenic/Likely pathogenic ★★ same condition
BBS2 p.Arg403fs Pathogenic/Likely pathogenic ★★ same condition
BBS2 p.Leu367fs Pathogenic/Likely pathogenic ★★ same condition
BBS2 p.Leu62fs Likely pathogenic ★★ same condition
BBS2 p.Thr555fs Pathogenic/Likely pathogenic ★★ same condition
BBS2 p.Val94fs 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-asn663ter (accessed [today's date]).

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