Is IFITM5 p.Pro29= (c.87G>A) pathogenic?

IFITM5 p.Pro29= (c.87G>A) is classified Benign/Likely benign in IFITM5 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-07). Rare (popmax 0.488%, sas); Associated with osteogenesis imperfecta.

What condition is associated with IFITM5 p.Pro29= (c.87G>A)?

IFITM5 p.Pro29= (c.87G>A) is associated with osteogenesis imperfecta (ClinVar).

How common is IFITM5 p.Pro29= (c.87G>A) in the general population?

IFITM5 p.Pro29= (c.87G>A) is rare (popmax 0.488%, sas) (gnomAD).

How is Osteogenesis imperfecta inherited?

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

IFITM5 p.Pro29=

c.87G>A · rs372443030 · VCV513279

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.488%, 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 -7	GERP -2.6
Overall
CADD	1.213	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.488% South Asian · 412/84,454 alleles

Filtering AF 0.449% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.434%

Overall 0.135% 2,113/1,562,274 alleles · rare exomes 2,003/1,410,154 · genomes 110/152,120 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.488%	205
Remaining individualsnot grpmax-eligible	0.137%	728
European (non-Finnish)	0.133%	751
Admixed American	0.0646%	1,548
African / African-American	0.0521%	1,919
Middle Eastern	0.0339%	2,954
East Asian	0.0096%	10,414
Finnishnot grpmax-eligible	0.00167%	59,980

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: IFITM5
Protein: p.Pro29=
Coding: c.87G>A
MANE Select: NM_001025295
dbSNP: rs372443030
Type: single nucleotide variant
Location: chr11:299404 (GRCh38)
Gene constraint: LOEUF 1.83 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.49

Full IFITM5 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

IFITM5 p.Pro29Leu Benign ★ same residue
IFITM5 c.-14C>T Pathogenic ★★ same condition
IFITM5 p.Ala23Val Uncertain significance ★★ ⚠ same condition
IFITM5 p.Asp128= Benign ★★ same condition
IFITM5 p.Ser40= Benign ★★ same condition
IFITM5 p.Thr14= Benign/Likely benign ★★ same condition
IFITM5 c.-3C>T Conflicting classifications of pathogenicity ★ same condition
IFITM5 p.Ala12Ser Conflicting classifications of pathogenicity ★ ⚠ 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/ifitm5-p-pro29 (accessed [today's date]).

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