Is BBS5 p.Glu9Asp (c.27G>T) pathogenic?

BBS5 p.Glu9Asp (c.27G>T) is classified Uncertain significance in BBS5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-25). AlphaMissense: likely pathogenic (0.9366); Very rare (popmax 0.00153%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BBS5 p.Glu9Asp (c.27G>T)?

BBS5 p.Glu9Asp (c.27G>T) is associated with Inborn genetic diseases (ClinVar).

How common is BBS5 p.Glu9Asp (c.27G>T) in the general population?

BBS5 p.Glu9Asp (c.27G>T) is very rare (popmax 0.00153%, nfe) (gnomAD).

What do computational predictors say about BBS5 p.Glu9Asp (c.27G>T)?

AlphaMissense predicts likely pathogenic (score 0.9366) — an in-silico prediction, not a clinical call.

BBS5 p.Glu9Asp

c.27G>T · rs1454907698 · VCV2319469

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9366 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9366	likely pathogenic
REVEL	0.613	indeterminate
SaProt	LLR -9.26	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP -2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 25 kb · p 0.023 · regional, not allelic
Overall
CADD	21.9	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 0.00153% European (non-Finnish) · 18/1,180,018 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00112% 18/1,614,072 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: BBS5
Protein: p.Glu9Asp
Coding: c.27G>T
MANE Select: NM_152384
dbSNP: rs1454907698
Type: single nucleotide variant
Location: chr2:169479580 (GRCh38)
Gene constraint: LOEUF 0.884 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.87 · 1 PDB

Full BBS5 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

BBS5 p.Glu9Lys Uncertain significance ★★ ⚠ same residue
BBS5 p.Glu9Gln Uncertain significance ★ same residue
BBS5 p.Arg11Gln Uncertain significance ★★ ⚠ same condition
BBS5 p.Arg312His Uncertain significance ★★ ⚠ same condition
BBS5 p.Asn74Thr Uncertain significance ★★ ⚠ same condition
BBS5 p.Cys101Tyr Uncertain significance ★★ ⚠ same condition
BBS5 p.Gly45Arg Uncertain significance ★★ ⚠ same condition
BBS5 p.Phe299Ser 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/bbs5-p-glu9asp (accessed [today's date]).

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