IFT122 p.Pro1065=
c.3195G>A · rs372233532 · VCV2731515
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0155%, sas)
Conditions
1
cranioectodermal dysplasia 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -12 | GERP -3.6 |
| Overall | ||
| CADD | 4.97 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0155%
South Asian · 14/90,090 alleles
Filtering AF
0.00939%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00753%
Overall
0.00575%
91/1,582,626 alleles · ultra-rare
exomes 86/1,430,478 · genomes 5/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0155% | 6,435 |
| European (non-Finnish) | 0.0065% | 15,387 |
| Remaining individualsnot grpmax-eligible | 0.00163% | 61,236 |
| African / African-American | 0.00137% | 73,240 |
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
- IFT122
- Protein
- p.Pro1065=
- Coding
- c.3195G>A
- MANE Select
- NM_052989
- dbSNP
- rs372233532
- Type
- single nucleotide variant
- Location
- chr3:129515529 (GRCh38)
- Gene constraint
- LOEUF 0.811 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.91 · 5 PDB
Similar variants
- IFT122 p.Pro1065Leu Uncertain significance ★★ ⚠ same residue
- IFT122 c.1148-1G>C Pathogenic/Likely pathogenic ★★ same condition
- IFT122 c.272+1G>A Likely pathogenic ★★ same condition
- IFT122 c.273-257C>A Pathogenic/Likely pathogenic ★★ same condition
- IFT122 c.3265+1G>A Pathogenic/Likely pathogenic ★★ same condition
- IFT122 p.Arg1185Ter Pathogenic/Likely pathogenic ★★ same condition
- IFT122 p.Arg189Ter Pathogenic/Likely pathogenic ★★ same condition
- IFT122 p.Arg673Ter Pathogenic/Likely pathogenic ★★ 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/ift122-p-pro1065 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown