Is BBS2 p.Ser405Cys (c.1214C>G) pathogenic?

BBS2 p.Ser405Cys (c.1214C>G) is classified Uncertain significance in BBS2 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-04-07). AlphaMissense: likely benign (0.0862); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BBS2 p.Ser405Cys (c.1214C>G)?

BBS2 p.Ser405Cys (c.1214C>G) is associated with Inborn genetic diseases (ClinVar).

How common is BBS2 p.Ser405Cys (c.1214C>G) in the general population?

BBS2 p.Ser405Cys (c.1214C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BBS2 p.Ser405Cys (c.1214C>G)?

AlphaMissense predicts likely benign (score 0.0862) — an in-silico prediction, not a clinical call.

BBS2 p.Ser405Cys

c.1214C>G · rs1355204201 · VCV2535317

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0862 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0862	likely benign
REVEL	0.682	pathogenic-leaning
SaProt	LLR -10.01	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 35 kb · p 9.6e-05 · regional, not allelic
Overall
CADD	21.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BBS2
Protein: p.Ser405Cys
Coding: c.1214C>G
MANE Select: NM_031885
dbSNP: rs1355204201
Type: single nucleotide variant
Location: chr16:56501364 (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

Similar variants

BBS2 p.Ser405= Likely benign ★ same residue
BBS2 p.Ala682Thr Uncertain significance ★★ ⚠ same condition
BBS2 p.Arg353Cys Uncertain significance ★★ ⚠ same condition
BBS2 p.Arg374Gln Uncertain significance ★★ ⚠ same condition
BBS2 p.Arg539Gln Uncertain significance ★★ ⚠ same condition
BBS2 p.Arg622Gln Uncertain significance ★★ ⚠ same condition
BBS2 p.Arg661His Uncertain significance ★★ ⚠ same condition
BBS2 p.Arg684His Uncertain significance ★★ ⚠ 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-ser405cys (accessed [today's date]).

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