Is SDCCAG8 p.Arg22= (c.66G>T) pathogenic?

SDCCAG8 p.Arg22= (c.66G>T) is classified Uncertain significance in SDCCAG8 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-07-17). Very rare (popmax 0.004%, afr); Associated with Bardet-Biedl syndrome 16.

What condition is associated with SDCCAG8 p.Arg22= (c.66G>T)?

SDCCAG8 p.Arg22= (c.66G>T) is associated with Bardet-Biedl syndrome 16, Senior-Loken syndrome 7 (ClinVar).

How common is SDCCAG8 p.Arg22= (c.66G>T) in the general population?

SDCCAG8 p.Arg22= (c.66G>T) is very rare (popmax 0.004%, afr) (gnomAD).

How is Bardet-Biedl syndrome inherited?

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

SDCCAG8 p.Arg22=

c.66G>T · rs764668676 · VCV969829

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

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 12	GERP 1.9, phastCons 1
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,948 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.0013% 21/1,613,990 alleles · very rare exomes 17/1,461,746 · genomes 4/152,244 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,983
Admixed American	0.00167%	60,010
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.00136%	73,746

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.Arg22=
Coding: c.66G>T
MANE Select: NM_006642
dbSNP: rs764668676
Type: single nucleotide variant
Location: chr1:243256239 (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.Arg22Trp Uncertain significance ★★ ⚠ same residue
SDCCAG8 p.Arg22Gly 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

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-arg22 (accessed [today's date]).

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