Is BBS2 p.Val19Met (c.55G>A) pathogenic?

BBS2 p.Val19Met (c.55G>A) is classified Uncertain significance in BBS2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-16). AlphaMissense: ambiguous (0.4528); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with BBS2 p.Val19Met (c.55G>A)?

BBS2 p.Val19Met (c.55G>A) is associated with Inborn genetic diseases, Bardet-Biedl syndrome 2, Bardet-Biedl syndrome (ClinVar).

How common is BBS2 p.Val19Met (c.55G>A) in the general population?

BBS2 p.Val19Met (c.55G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about BBS2 p.Val19Met (c.55G>A)?

AlphaMissense predicts ambiguous (score 0.4528) — an in-silico prediction, not a clinical call.

BBS2 p.Val19Met

c.55G>A · rs1158566793 · VCV1006657

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.4528 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4528	ambiguous
REVEL	0.396	indeterminate
SaProt	LLR -7.87	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 9.6e-05 · regional, not allelic
Overall
CADD	27.9	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 · 1/59,998 alleles

Overall 6.84e-05% 1/1,461,494 alleles · very rare

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.Val19Met
Coding: c.55G>A
MANE Select: NM_031885
dbSNP: rs1158566793
Type: single nucleotide variant
Location: chr16:56519808 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bardet-Biedl syndrome 2 Bardet-Biedl syndrome

Similar variants

BBS2 p.Val19Leu Uncertain significance ★ ⚠ same residue
BBS2 p.Val19= Likely benign ★ same residue
BBS2 p.Val19fs Likely pathogenic 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

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-val19met (accessed [today's date]).

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