Is CRTAP p.Pro94= (c.282C>T) pathogenic?

CRTAP p.Pro94= (c.282C>T) is classified Conflicting classifications of pathogenicity in CRTAP (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-17). Ultra-rare (popmax 0.0328%, afr); Associated with osteogenesis imperfecta.

What condition is associated with CRTAP p.Pro94= (c.282C>T)?

CRTAP p.Pro94= (c.282C>T) is associated with osteogenesis imperfecta, osteogenesis imperfecta type 7 (ClinVar).

How common is CRTAP p.Pro94= (c.282C>T) in the general population?

CRTAP p.Pro94= (c.282C>T) is ultra-rare (popmax 0.0328%, afr) (gnomAD).

How is Osteogenesis imperfecta inherited?

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

CRTAP p.Pro94=

c.282C>T · rs540998437 · VCV344806

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0328%, afr)

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 -0.21	GERP -1.6, phastCons 0.33
Overall
CADD	8.482	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0328% African / African-American · 23/70,216 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0189%

Overall 0.00368% 56/1,522,416 alleles · ultra-rare exomes 50/1,370,272 · genomes 6/152,144 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0328%	3,053
Middle Eastern	0.0216%	4,640
Remaining individualsnot grpmax-eligible	0.0203%	4,932
European (non-Finnish)	0.00175%	57,069

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: CRTAP
Protein: p.Pro94=
Coding: c.282C>T
MANE Select: NM_006371
dbSNP: rs540998437
Type: single nucleotide variant
Location: chr3:33114359 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.81 · 6 PDB
Residue 94: an α-helix

Full CRTAP 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

Also linked: osteogenesis imperfecta type 7

For Osteogenesis imperfecta (Orphanet):

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

Similar variants

CRTAP p.Pro94Ser Uncertain significance ★ ⚠ same residue
CRTAP c.471+2C>A Pathogenic/Likely pathogenic ★★ same condition
CRTAP p.Arg212Ter Pathogenic/Likely pathogenic ★★ same condition
CRTAP p.Gln276Ter Pathogenic ★★ same condition
CRTAP p.Tyr148Ter Pathogenic/Likely pathogenic ★★ same condition
CRTAP p.Tyr340Ter Pathogenic/Likely pathogenic ★★ same condition
CRTAP p.Tyr66Ter Pathogenic ★★ same condition
CRTAP c.*3221C>T 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/crtap-p-pro94 (accessed [today's date]).

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