Is BBS2 p.Arg632Pro (c.1895G>C) pathogenic?

BBS2 p.Arg632Pro (c.1895G>C) is classified Pathogenic/Likely pathogenic in BBS2 (ClinVar, Multiple submitters, 21 submitters; last evaluated 2026-01-19). AlphaMissense: likely pathogenic (0.988); Very rare (popmax 0.000848%, nfe); Associated with Autosomal recessive BBS2-related disorders.

What condition is associated with BBS2 p.Arg632Pro (c.1895G>C)?

BBS2 p.Arg632Pro (c.1895G>C) is associated with Autosomal recessive BBS2-related disorders, Bardet-Biedl syndrome 2, retinitis pigmentosa 74 (ClinVar).

How common is BBS2 p.Arg632Pro (c.1895G>C) in the general population?

BBS2 p.Arg632Pro (c.1895G>C) is very rare (popmax 0.000848%, nfe) (gnomAD).

What do computational predictors say about BBS2 p.Arg632Pro (c.1895G>C)?

AlphaMissense predicts likely pathogenic (score 0.988) — an in-silico prediction, not a clinical call.

BBS2 p.Arg632Pro

c.1895G>C · rs138043021 · VCV4578

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 21 submitters

AlphaMissense

likely pathogenic

0.988 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000848%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Autosomal recessive BBS2-related disorders

Computational evidence

Protein change
AlphaMissense	0.988	likely pathogenic ✓ concordant with ClinVar · top 3% in BBS2
REVEL	0.952	strongly pathogenic-leaning
SaProt	LLR -17.88	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 9.6e-05 · regional, not allelic
Overall
CADD	29.5	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 0.000848% European (non-Finnish) · 10/1,179,470 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.00663% 107/1,613,452 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.267%	375
Remaining individualsnot grpmax-eligible	0.0272%	3,674
Finnishnot grpmax-eligible	0.00156%	64,026
European (non-Finnish)grpmax	0.000848%	117,947

Ashkenazi Jewish 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.Arg632Pro
Coding: c.1895G>C
MANE Select: NM_031885
dbSNP: rs138043021
Type: single nucleotide variant
Location: chr16:56496982 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49
Residue 632: a UniProt-annotated variant site (in bbs2 and rp74)

Full BBS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Autosomal recessive BBS2-related disorders

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

Similar variants

BBS2 p.Arg632His Uncertain significance ★★ ⚠ same residue
BBS2 p.Arg632Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
BBS2 c.118-1G>T Likely pathogenic ★★ same condition
BBS2 c.118-2A>C Likely pathogenic ★★ same condition
BBS2 c.118-2A>G Likely pathogenic ★★ same condition
BBS2 c.1225+2T>C Likely pathogenic ★★ same condition
BBS2 c.1225+2T>G Likely pathogenic ★★ same condition
BBS2 c.1397+1G>A 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/bbs2-p-arg632pro (accessed [today's date]).

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