Is CRTAP p.Phe303= (c.909T>C) pathogenic?

CRTAP p.Phe303= (c.909T>C) is classified Likely benign in CRTAP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-30). Very rare (popmax 8.48e-05%, nfe); Associated with osteogenesis imperfecta type 7.

What condition is associated with CRTAP p.Phe303= (c.909T>C)?

CRTAP p.Phe303= (c.909T>C) is associated with osteogenesis imperfecta type 7 (ClinVar).

How common is CRTAP p.Phe303= (c.909T>C) in the general population?

CRTAP p.Phe303= (c.909T>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

CRTAP p.Phe303=

c.909T>C · rs1437997214 · VCV2910807

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, 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 -2.9	GERP -2.5
Overall
CADD	6.871	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,762 alleles

Overall 6.2e-05% 1/1,613,818 alleles · very rare exomes 1/1,461,492 · genomes 0/152,326 · joint denominator

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.Phe303=
Coding: c.909T>C
MANE Select: NM_006371
dbSNP: rs1437997214
Type: single nucleotide variant
Location: chr3:33130054 (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 303: an α-helix

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 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
CRTAP c.*703A>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-phe303 (accessed [today's date]).

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