Is BBS2 p.Val40Phe (c.118G>T) pathogenic?

BBS2 p.Val40Phe (c.118G>T) is classified Conflicting classifications of pathogenicity in BBS2 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-08). AlphaMissense: likely pathogenic (0.7621); Very rare (popmax 0.00267%, afr); Associated with BBS2-related disorder.

What condition is associated with BBS2 p.Val40Phe (c.118G>T)?

BBS2 p.Val40Phe (c.118G>T) is associated with BBS2-related disorder, Bardet-Biedl syndrome 2, retinitis pigmentosa 74 (ClinVar).

How common is BBS2 p.Val40Phe (c.118G>T) in the general population?

BBS2 p.Val40Phe (c.118G>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about BBS2 p.Val40Phe (c.118G>T)?

AlphaMissense predicts likely pathogenic (score 0.7621) — an in-silico prediction, not a clinical call.

BBS2 p.Val40Phe

c.118G>T · rs886043059 · VCV285263

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.7621 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

BBS2-related disorder

Computational evidence

Protein change
AlphaMissense	0.7621	likely pathogenic
REVEL	0.877	moderately pathogenic-leaning
SaProt	LLR -8.96	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 9.6e-05 · regional, not allelic
Overall
CADD	28.4	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 0.00267% African / African-American · 2/74,796 alleles

Filtering AF 0.000766% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000607%

Overall 0.00118% 19/1,609,324 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,398
East Asian	0.00223%	44,872
Admixed American	0.00167%	59,860
European (non-Finnish)	0.00128%	78,414

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.Val40Phe
Coding: c.118G>T
MANE Select: NM_031885
dbSNP: rs886043059
Type: single nucleotide variant
Location: chr16:56514680 (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.Val40Gly Uncertain significance ★ ⚠ 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
BBS2 c.1397+2T>C 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-val40phe (accessed [today's date]).

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