IFT122 p.Ser460=
c.1380C>T · rs142641511 · VCV1183155
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.151%, mid)
Conditions
1
cranioectodermal dysplasia 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.065 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -13 | GERP -4.2 |
| Overall | ||
| CADD | 2.897 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.151%
Middle Eastern · 9/5,970 alleles
Filtering AF
0.0786%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0587%
Overall
0.0133%
214/1,613,908 alleles · rare
exomes 179/1,461,724 · genomes 35/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.151% | 663 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0642% | 1,558 |
| South Asian | 0.0593% | 1,687 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,472 |
| Admixed American | 0.0217% | 4,617 |
| African / African-American | 0.0213% | 4,686 |
| East Asian | 0.0134% | 7,479 |
| European (non-Finnish) | 0.0067% | 14,936 |
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.Ser460=
- Coding
- c.1380C>T
- MANE Select
- NM_052989
- dbSNP
- rs142641511
- Type
- single nucleotide variant
- Location
- chr3:129479814 (GRCh38)
- Gene constraint
- LOEUF 0.811 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.91 · 5 PDB
Similar variants
- IFT122 p.Ser460Cys 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-ser460 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown