Is BBS1 p.Ala2Ser (c.4G>T) pathogenic?

BBS1 p.Ala2Ser (c.4G>T) is classified Uncertain significance in BBS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-08). AlphaMissense: likely benign (0.1455); Absent from gnomAD v4.1.

How common is BBS1 p.Ala2Ser (c.4G>T) in the general population?

BBS1 p.Ala2Ser (c.4G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BBS1 p.Ala2Ser (c.4G>T)?

AlphaMissense predicts likely benign (score 0.1455) — an in-silico prediction, not a clinical call.

BBS1 p.Ala2Ser

c.4G>T · VCV4912380

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1455 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1455	likely benign
REVEL	0.473	indeterminate
SaProt	LLR -7.42	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 21 kb · p 0.059 · regional, not allelic
Overall
CADD	19.96	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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: BBS1
Protein: p.Ala2Ser
Coding: c.4G>T
MANE Select: NM_024649
Type: single nucleotide variant
Location: chr11:66510663 (GRCh38)
Gene constraint: LOEUF 1.003 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.05 · 1 PDB
Residue 2: a modified residue (n-acetylalanine)

Full BBS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BBS1 p.Ala2= Likely benign ★★ same residue
BBS1 c.1110+3G>C Pathogenic/Likely pathogenic ★★ same type
BBS1 c.1111-2A>G Likely pathogenic ★★ same type
BBS1 c.1181-9C>G Pathogenic/Likely pathogenic ★★ same type
BBS1 c.124+1G>A Pathogenic ★★ same type
BBS1 c.124+1G>C Pathogenic/Likely pathogenic ★★ same type
BBS1 c.159+1G>A Likely pathogenic ★★ same type
BBS1 c.1608+1G>A Pathogenic/Likely pathogenic ★★ same type

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/bbs1-p-ala2ser (accessed [today's date]).

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