Is SDCCAG8 p.Pro66= (c.198C>T) pathogenic?

SDCCAG8 p.Pro66= (c.198C>T) is classified Likely benign in SDCCAG8 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-09). Very rare (popmax 0.00223%, eas); Associated with Senior-Loken syndrome 7.

What condition is associated with SDCCAG8 p.Pro66= (c.198C>T)?

SDCCAG8 p.Pro66= (c.198C>T) is associated with Senior-Loken syndrome 7, Bardet-Biedl syndrome 16 (ClinVar).

How common is SDCCAG8 p.Pro66= (c.198C>T) in the general population?

SDCCAG8 p.Pro66= (c.198C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Senior-Loken syndrome inherited?

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

SDCCAG8 p.Pro66=

c.198C>T · rs201715098 · VCV1079154

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Senior-Loken syndrome 7

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 -8.3	GERP -3.6
Overall
CADD	0.684	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,874 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00112% 18/1,614,032 alleles · very rare exomes 16/1,461,802 · genomes 2/152,230 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,874
Admixed American	0.00167%	60,006
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	0.00127%	78,666

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.Pro66=
Coding: c.198C>T
MANE Select: NM_006642
dbSNP: rs201715098
Type: single nucleotide variant
Location: chr1:243270235 (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

Senior-Loken syndrome 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bardet-Biedl syndrome 16

For Senior-Loken syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

SDCCAG8 p.Pro66Leu 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-pro66 (accessed [today's date]).

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