Is SDCCAG8 p.Ser166= (c.498T>G) pathogenic?

SDCCAG8 p.Ser166= (c.498T>G) is classified Likely benign in SDCCAG8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-12). Ultra-rare (popmax 0.0362%, sas); Associated with Bardet-Biedl syndrome 16.

What condition is associated with SDCCAG8 p.Ser166= (c.498T>G)?

SDCCAG8 p.Ser166= (c.498T>G) is associated with Bardet-Biedl syndrome 16, Senior-Loken syndrome 7 (ClinVar).

How common is SDCCAG8 p.Ser166= (c.498T>G) in the general population?

SDCCAG8 p.Ser166= (c.498T>G) is ultra-rare (popmax 0.0362%, sas) (gnomAD).

How is Bardet-Biedl syndrome inherited?

Typically Autosomal recessive, Oligogenic (Orphanet). A genetic counselor can assess individual risk for a family.

SDCCAG8 p.Ser166=

c.498T>G · rs762183907 · VCV1135677

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0362%, sas)

Conditions

Bardet-Biedl syndrome 16

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP 0.091, phastCons 0.99
Overall
CADD	10.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0362% South Asian · 33/91,074 alleles

Filtering AF 0.0265% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0231%

Overall 0.00235% 38/1,613,976 alleles · ultra-rare exomes 38/1,461,674 · genomes 0/152,302 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0362%	2,760
Remaining individualsnot grpmax-eligible	0.0048%	20,832
European (non-Finnish)	0.00017%	589,936

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: SDCCAG8
Protein: p.Ser166=
Coding: c.498T>G
MANE Select: NM_006642
dbSNP: rs762183907
Type: single nucleotide variant
Location: chr1:243286349 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.67

Full SDCCAG8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bardet-Biedl syndrome 16 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Senior-Loken syndrome 7

For Bardet-Biedl syndrome (Orphanet):

Inheritance: Autosomal recessive, Oligogenic
Onset: Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Specific population)

Similar variants

SDCCAG8 p.Ser166Cys Uncertain significance ★ ⚠ same residue
SDCCAG8 c.1356+1G>C Likely pathogenic ★★ same condition
SDCCAG8 c.221-2A>G Pathogenic ★★ same condition
SDCCAG8 c.420+1G>C Likely pathogenic ★★ same condition
SDCCAG8 c.546+1G>A Likely pathogenic ★★ same condition
SDCCAG8 c.740+356C>T Pathogenic/Likely pathogenic ★★ same condition
SDCCAG8 p.Arg374Ter Pathogenic/Likely pathogenic ★★ same condition
SDCCAG8 p.Gln161Ter 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/sdccag8-p-ser166 (accessed [today's date]).

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