Is BBS5 p.Val300= (c.900G>C) pathogenic?

BBS5 p.Val300= (c.900G>C) is classified Uncertain significance in BBS5 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2022-06-27). Very rare (popmax 0.00307%, nfe); Associated with inherited retinal dystrophy.

What condition is associated with BBS5 p.Val300= (c.900G>C)?

BBS5 p.Val300= (c.900G>C) is associated with inherited retinal dystrophy, cone dystrophy, Bardet-Biedl syndrome 5 (ClinVar).

How common is BBS5 p.Val300= (c.900G>C) in the general population?

BBS5 p.Val300= (c.900G>C) is very rare (popmax 0.00307%, nfe) (gnomAD).

BBS5 p.Val300=

c.900G>C · rs757001492 · VCV437994

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00307%, nfe)

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Pangolin	Δ0.70	loss · gain 0.01 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 8.4	GERP 1.4, phastCons 1
Overall
CADD	20.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00307% European (non-Finnish) · 36/1,173,956 alleles

Filtering AF 0.00225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00199%

Overall 0.00243% 39/1,607,098 alleles · very rare exomes 38/1,454,940 · genomes 1/152,158 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00307%	32,610
African / African-American	0.00268%	37,374
Remaining individualsnot grpmax-eligible	0.00161%	62,264

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.Val300=
Coding: c.900G>C
MANE Select: NM_152384
dbSNP: rs757001492
Type: single nucleotide variant
Location: chr2:169503178 (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

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cone dystrophy Bardet-Biedl syndrome 5 Bardet-Biedl syndrome

Similar variants

BBS5 p.Val300Leu Uncertain significance ★ ⚠ same residue
BBS5 p.Val300fs Likely pathogenic ★ same residue
BBS5 c.143-1G>C Pathogenic/Likely pathogenic ★★ same condition
BBS5 c.209-1G>A Pathogenic/Likely pathogenic ★★ same condition
BBS5 c.209-2A>G Likely pathogenic ★★ same condition
BBS5 c.522+3A>G Pathogenic/Likely pathogenic ★★ same condition
BBS5 c.681+1G>T Pathogenic/Likely pathogenic ★★ same condition
BBS5 p.Arg138Cys 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/bbs5-p-val300 (accessed [today's date]).

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