Is CRTAP p.Phe153Leu (c.459C>G) pathogenic?

CRTAP p.Phe153Leu (c.459C>G) is classified Uncertain significance in CRTAP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-15). AlphaMissense: likely pathogenic (0.9717); Ultra-rare (popmax 0.0978%, sas); Associated with osteogenesis imperfecta type 7.

What condition is associated with CRTAP p.Phe153Leu (c.459C>G)?

CRTAP p.Phe153Leu (c.459C>G) is associated with osteogenesis imperfecta type 7 (ClinVar).

How common is CRTAP p.Phe153Leu (c.459C>G) in the general population?

CRTAP p.Phe153Leu (c.459C>G) is ultra-rare (popmax 0.0978%, sas) (gnomAD).

What do computational predictors say about CRTAP p.Phe153Leu (c.459C>G)?

AlphaMissense predicts likely pathogenic (score 0.9717) — an in-silico prediction, not a clinical call.

CRTAP p.Phe153Leu

c.459C>G · rs531119589 · VCV969457

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9717 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0978%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

osteogenesis imperfecta type 7

Computational evidence

Protein change
AlphaMissense	0.9717	likely pathogenic
REVEL	0.399	indeterminate
SaProt	LLR -9.67	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP 0.9, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 28 kb · p 0.00062 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0978% South Asian · 87/88,950 alleles

Filtering AF 0.0812% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0751%

Overall 0.00594% 95/1,599,966 alleles · ultra-rare exomes 89/1,447,648 · genomes 6/152,318 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0978%	1,022
Remaining individualsnot grpmax-eligible	0.00485%	20,597
East Asian	0.00449%	22,247
European (non-Finnish)	0.000255%	391,676

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.Phe153Leu
Coding: c.459C>G
MANE Select: NM_006371
dbSNP: rs531119589
Type: single nucleotide variant
Location: chr3:33114536 (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 153: 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 p.Phe153= Likely benign ★ 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-phe153leu (accessed [today's date]).

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