Is BBS7 p.Glu596Lys (c.1786G>A) pathogenic?

BBS7 p.Glu596Lys (c.1786G>A) is classified Conflicting classifications of pathogenicity in BBS7 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-05-23). AlphaMissense: likely benign (0.1681); Very rare (popmax 0.00224%, eas); Associated with BBS7-related disorder.

What condition is associated with BBS7 p.Glu596Lys (c.1786G>A)?

BBS7 p.Glu596Lys (c.1786G>A) is associated with BBS7-related disorder, Bardet-Biedl syndrome 7, Bardet-Biedl syndrome (ClinVar).

How common is BBS7 p.Glu596Lys (c.1786G>A) in the general population?

BBS7 p.Glu596Lys (c.1786G>A) is very rare (popmax 0.00224%, eas) (gnomAD).

What do computational predictors say about BBS7 p.Glu596Lys (c.1786G>A)?

AlphaMissense predicts likely benign (score 0.1681) — an in-silico prediction, not a clinical call.

BBS7 p.Glu596Lys

c.1786G>A · rs1233058112 · VCV812228

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1681 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00224%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

BBS7-related disorder

Computational evidence

Protein change
AlphaMissense	0.1681	likely benign
REVEL	0.545	indeterminate
SaProt	LLR -6.89	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.86	donor loss at this position · masked 0 · deltas
Pangolin	Δ0.58	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 44 kb · p 0.00015 · regional, not allelic
Overall
CADD	34.0	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 0.00224% East Asian · 1/44,580 alleles

Overall 0.00021% 3/1,428,206 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00224%	44,580
Admixed American	0.00167%	59,932
South Asian	0.00111%	90,326

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: BBS7
Protein: p.Glu596Lys
Coding: c.1786G>A
MANE Select: NM_176824
dbSNP: rs1233058112
Type: single nucleotide variant
Location: chr4:121828619 (GRCh38)
Gene constraint: LOEUF 0.701 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.99

Full BBS7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

BBS7-related disorder

Also linked: Bardet-Biedl syndrome 7 Bardet-Biedl syndrome

Similar variants

BBS7 p.Glu596Asp Uncertain significance ★★ ⚠ same residue
BBS7 c.1305+2T>A Likely pathogenic ★★ same condition
BBS7 c.1371+1G>A Likely pathogenic ★★ same condition
BBS7 c.1512-1G>A Likely pathogenic ★★ same condition
BBS7 c.1677-2A>G Pathogenic/Likely pathogenic ★★ same condition
BBS7 c.1891-2A>C Pathogenic/Likely pathogenic ★★ same condition
BBS7 c.342-2A>G Pathogenic/Likely pathogenic ★★ same condition
BBS7 c.529-2A>G Pathogenic/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/bbs7-p-glu596lys (accessed [today's date]).

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