Is SDCCAG8 p.Ser89= (c.267T>C) pathogenic?

SDCCAG8 p.Ser89= (c.267T>C) is classified Conflicting classifications of pathogenicity in SDCCAG8 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-26). Rare (popmax 0.11%, nfe); Associated with Senior-Loken syndrome 7.

What condition is associated with SDCCAG8 p.Ser89= (c.267T>C)?

SDCCAG8 p.Ser89= (c.267T>C) is associated with Senior-Loken syndrome 7, Bardet-Biedl syndrome 16 (ClinVar).

How common is SDCCAG8 p.Ser89= (c.267T>C) in the general population?

SDCCAG8 p.Ser89= (c.267T>C) is rare (popmax 0.11%, nfe) (gnomAD).

How is Senior-Loken syndrome inherited?

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

SDCCAG8 p.Ser89=

c.267T>C · rs148818431 · VCV167663

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.11%, nfe)

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 1.2	GERP 2.2, phastCons 0.92
Overall
CADD	9.671	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.11% European (non-Finnish) · 1,301/1,179,692 alleles

Filtering AF 0.105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.103%

Overall 0.0943% 1,522/1,613,524 alleles · rare exomes 1,423/1,461,402 · genomes 99/152,122 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.385%	260
European (non-Finnish)grpmax	0.11%	907
Remaining individualsnot grpmax-eligible	0.0736%	1,358
Admixed American	0.0684%	1,463
Middle Eastern	0.0329%	3,040
African / African-American	0.0214%	4,682
Finnishnot grpmax-eligible	0.00312%	32,006

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser89=
Coding: c.267T>C
MANE Select: NM_006642
dbSNP: rs148818431
Type: single nucleotide variant
Location: chr1:243271024 (GRCh38)
Gene constraint: LOEUF 0.843 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.67
Residue 89: the 'disordered' 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-ser89 (accessed [today's date]).

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