Is CRTAP p.Pro176= (c.528T>G) pathogenic?

CRTAP p.Pro176= (c.528T>G) is classified Conflicting classifications of pathogenicity in CRTAP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-10-30). Very rare (popmax 0.00297%, nfe); Associated with osteogenesis imperfecta type 7.

What condition is associated with CRTAP p.Pro176= (c.528T>G)?

CRTAP p.Pro176= (c.528T>G) is associated with osteogenesis imperfecta type 7 (ClinVar).

How common is CRTAP p.Pro176= (c.528T>G) in the general population?

CRTAP p.Pro176= (c.528T>G) is very rare (popmax 0.00297%, nfe) (gnomAD).

CRTAP p.Pro176=

c.528T>G · rs774680682 · VCV900859

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00297%, nfe)

Conditions

osteogenesis imperfecta type 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 -9.9	GERP -3.5
Overall
CADD	0.692	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00297% European (non-Finnish) · 35/1,179,990 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00223% 36/1,614,042 alleles · very rare exomes 34/1,461,832 · genomes 2/152,210 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00297%	33,714
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Pro176=
Coding: c.528T>G
MANE Select: NM_006371
dbSNP: rs774680682
Type: single nucleotide variant
Location: chr3:33120400 (GRCh38)
Gene constraint: LOEUF 1.251 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.81 · 6 PDB

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

Disease context

osteogenesis imperfecta type 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRTAP p.Pro176His 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-pro176 (accessed [today's date]).

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