Is SP7 p.Ala285= (c.855G>A) pathogenic?

SP7 p.Ala285= (c.855G>A) is classified Conflicting classifications of pathogenicity in SP7 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-04-17). Ultra-rare (popmax 0.0538%, sas); Associated with osteogenesis imperfecta.

What condition is associated with SP7 p.Ala285= (c.855G>A)?

SP7 p.Ala285= (c.855G>A) is associated with osteogenesis imperfecta (ClinVar).

How common is SP7 p.Ala285= (c.855G>A) in the general population?

SP7 p.Ala285= (c.855G>A) is ultra-rare (popmax 0.0538%, sas) (gnomAD).

How is Osteogenesis imperfecta inherited?

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

SP7 p.Ala285=

c.855G>A · rs561083858 · VCV1702065

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0538%, sas)

Conditions

osteogenesis imperfecta

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 -11	GERP -3.7
Overall
CADD	0.384	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0538% South Asian · 49/90,994 alleles

Filtering AF 0.0418% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0375%

Overall 0.00454% 73/1,609,334 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0538%	1,857
Remaining individualsnot grpmax-eligible	0.00965%	10,362
East Asian	0.00223%	44,744
European (non-Finnish)	0.00136%	73,546
African / African-American	0.00133%	74,970

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.Ala285=
Coding: c.855G>A
MANE Select: NM_001173467
dbSNP: rs561083858
Type: single nucleotide variant
Location: chr12:53328587 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Osteogenesis imperfecta (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Worldwide)

Similar variants

SP7 p.Arg267Cys Uncertain significance ★★ ⚠ same condition
SP7 p.Arg280Leu Uncertain significance ★★ ⚠ same condition
SP7 p.Cys331= Benign ★★ same condition
SP7 p.Leu288= Benign/Likely benign ★★ same condition
SP7 p.Arg395His Conflicting classifications of pathogenicity ★ ⚠ same condition
SP7 p.Asp62Tyr Uncertain significance ★ ⚠ same condition
SP7 p.Pro225= Uncertain significance ★ same condition
SP7 p.Trp167Ter Uncertain significance ★ 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-ala285 (accessed [today's date]).

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