IFT122 p.Pro331=
c.993G>A · rs775251218 · VCV2041577
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, amr)
Conditions
1
cranioectodermal dysplasia 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.06 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -4.5 |
| Overall | ||
| CADD | 1.171 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Admixed American · 10/59,992 alleles
Filtering AF
0.009%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00681%
Overall
0.00161%
26/1,613,990 alleles · ultra-rare
exomes 20/1,461,878 · genomes 6/152,112 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0167% | 5,999 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,238 |
| African / African-American | 0.00267% | 37,451 |
| South Asian | 0.0011% | 91,068 |
| European (non-Finnish) | 0.000932% | 107,276 |
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.Pro331=
- Coding
- c.993G>A
- MANE Select
- NM_052989
- dbSNP
- rs775251218
- Type
- single nucleotide variant
- Location
- chr3:129476491 (GRCh38)
- Gene constraint
- LOEUF 0.811 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.91 · 5 PDB
Similar variants
- 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
- IFT122 p.Gln1005Ter 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-pro331 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown