Is SDCCAG8 p.Ser321= (c.963C>T) pathogenic?

SDCCAG8 p.Ser321= (c.963C>T) is classified Likely benign in SDCCAG8 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-14). Ultra-rare (popmax 0.0134%, eas); Associated with Senior-Loken syndrome 7.

What condition is associated with SDCCAG8 p.Ser321= (c.963C>T)?

SDCCAG8 p.Ser321= (c.963C>T) is associated with Senior-Loken syndrome 7, Bardet-Biedl syndrome 16 (ClinVar).

How common is SDCCAG8 p.Ser321= (c.963C>T) in the general population?

SDCCAG8 p.Ser321= (c.963C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

How is Senior-Loken syndrome inherited?

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

SDCCAG8 p.Ser321=

c.963C>T · rs751551796 · VCV1560106

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -8.6	GERP -3.6
Overall
CADD	0.908	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0134% East Asian · 6/44,882 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00192% 31/1,614,080 alleles · ultra-rare exomes 31/1,461,872 · genomes 0/152,208 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,480
South Asian	0.00549%	18,217
Admixed American	0.005%	20,005
African / African-American	0.00267%	37,490
European (non-Finnish)	0.00127%	78,668

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.Ser321=
Coding: c.963C>T
MANE Select: NM_006642
dbSNP: rs751551796
Type: single nucleotide variant
Location: chr1:243316788 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.67
Residue 321: the 'sufficient for homodimerization' region

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 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
SDCCAG8 p.Gln383Ter 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-ser321 (accessed [today's date]).

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