IFITM5 p.Ser40=
c.120G>T · rs79625057 · VCV193132
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.94%, eas)
Conditions
2
osteogenesis imperfecta type 5
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>T here scores Δ0.64 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -12 | GERP -3 |
| Overall | ||
| CADD | 0.478 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.94%
East Asian · 845/43,552 alleles
Filtering AF
1.83%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.79%
Overall
0.16%
2,554/1,596,362 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 1.94% | 52 |
| Admixed American | 1.89% | 53 |
| Finnishnot grpmax-eligible | 0.409% | 244 |
| Remaining individualsnot grpmax-eligible | 0.139% | 718 |
| South Asian | 0.121% | 827 |
| Middle Eastern | 0.0663% | 1,508 |
| African / African-American | 0.0323% | 3,095 |
| European (non-Finnish) | 0.0116% | 8,619 |
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.Ser40=
- Coding
- c.120G>T
- MANE Select
- NM_001025295
- dbSNP
- rs79625057
- Type
- single nucleotide variant
- Location
- chr11:299371 (GRCh38)
- Gene constraint
- LOEUF 1.83 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.49
- Residue 40
- a UniProt-annotated variant site (in oi5; correlates with reduced expression and barely detectable secretion of serpinf1)
Similar variants
- IFITM5 p.Ser40Leu Pathogenic ★★ same residue
- IFITM5 p.Ser40Trp Pathogenic/Likely pathogenic ★★ same residue
- IFITM5 p.Ser40Pro Uncertain significance ★ ⚠ same residue
- IFITM5 c.-14C>T Pathogenic ★★ same condition
- IFITM5 p.Ala23Val Uncertain significance ★★ ⚠ same condition
- IFITM5 p.Asn48Ser Uncertain significance ★★ same condition
- IFITM5 p.Asp128= Benign ★★ same condition
- IFITM5 p.Gly27Ala Benign ★★ 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-ser40 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown