Is SP7 p.Ser366= (c.1098C>T) pathogenic?

SP7 p.Ser366= (c.1098C>T) is classified Benign in SP7 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 98.6%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with osteogenesis imperfecta type 12.

What condition is associated with SP7 p.Ser366= (c.1098C>T)?

SP7 p.Ser366= (c.1098C>T) is associated with osteogenesis imperfecta type 12 (ClinVar).

SP7 p.Ser366=

Q: How common is SP7 p.Ser366= (c.1098C>T) in the general population?

SP7 p.Ser366= (c.1098C>T) is common (popmax 98.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1098C>T · rs7139272 · VCV285778

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 98.6%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

osteogenesis imperfecta type 12

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 -3.2	GERP -4.1
Overall
CADD	0.606	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 98.6% European (non-Finnish) · 1,161,657/1,178,638 alleles

Filtering AF 98.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 98.3%

Overall 97% 1,563,455/1,612,252 alleles · common exomes 1,425,092/1,460,006 · genomes 138,363/152,246 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	99.8%	1
Ashkenazi Jewishnot grpmax-eligible	99.1%	1
Amishnot grpmax-eligible	98.7%	1
European (non-Finnish)grpmax	98.6%	1
East Asian	97.6%	1
Admixed American	97.4%	1
Remaining individualsnot grpmax-eligible	96.3%	1
Middle Eastern	96%	1
South Asian	95.2%	1
African / African-American	70.9%	1

Finnish 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: SP7
Protein: p.Ser366=
Coding: c.1098C>T
MANE Select: NM_001173467
dbSNP: rs7139272
Type: single nucleotide variant
Location: chr12:53328344 (GRCh38)
Gene constraint: LOEUF 0.808 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 52.78

Full SP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

osteogenesis imperfecta type 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SP7 p.Arg365Ter Uncertain significance ★★ same condition
SP7 p.Arg407Gln Uncertain significance ★★ ⚠ same condition
SP7 p.Gly152Ala Uncertain significance ★★ ⚠ same condition
SP7 p.Tyr48Ter Uncertain significance ★★ same condition
SP7 p.Cys331= Benign ★★ same condition
SP7 p.His376= Benign ★★ same condition
SP7 p.Leu288= Benign/Likely benign ★★ same condition
SP7 p.Cys270Ter 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/sp7-p-ser366 (accessed [today's date]).

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