Is BBS2 p.Arg48Trp (c.142C>T) pathogenic?

BBS2 p.Arg48Trp (c.142C>T) is classified Uncertain significance in BBS2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-03-28). AlphaMissense: likely benign (0.12); Very rare (popmax 0.00167%, amr); Associated with retinitis pigmentosa 74.

What condition is associated with BBS2 p.Arg48Trp (c.142C>T)?

BBS2 p.Arg48Trp (c.142C>T) is associated with retinitis pigmentosa 74, Bardet-Biedl syndrome 2 (ClinVar).

How common is BBS2 p.Arg48Trp (c.142C>T) in the general population?

BBS2 p.Arg48Trp (c.142C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

How is Retinitis pigmentosa inherited?

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

What do computational predictors say about BBS2 p.Arg48Trp (c.142C>T)?

AlphaMissense predicts likely benign (score 0.12) — an in-silico prediction, not a clinical call.

BBS2 p.Arg48Trp

c.142C>T · rs1030249829 · VCV989966

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.12 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

retinitis pigmentosa 74

Computational evidence

Protein change
AlphaMissense	0.12	likely benign
REVEL	0.447	indeterminate
SaProt	LLR -11.84	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.50 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.8	GERP 0.75, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 9.6e-05 · regional, not allelic
Overall
CADD	27.2	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 0.00167% Admixed American · 1/60,004 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000479% 7/1,461,534 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,004
African / African-American	0.00133%	75,002
South Asian	0.0011%	91,054
European (non-Finnish)	0.000339%	294,936

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.Arg48Trp
Coding: c.142C>T
MANE Select: NM_031885
dbSNP: rs1030249829
Type: single nucleotide variant
Location: chr16:56514656 (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

retinitis pigmentosa 74 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bardet-Biedl syndrome 2

For Retinitis pigmentosa (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

BBS2 p.Arg48Gln Uncertain significance ★ ⚠ same residue
BBS2 p.Arg48= Likely benign ★ 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-arg48trp (accessed [today's date]).

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