CFAP251 p.Ile453=
c.1359C>T · rs61952863 · VCV1711359
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.02%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.24 | acceptor loss, 38 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.1 | GERP 0.85, phastCons 0.92 |
| Overall | ||
| CADD | 7.434 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.02%
Middle Eastern · 62/6,062 alleles
Filtering AF
0.819%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.745%
Overall
0.115%
1,852/1,614,156 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.02% | 98 |
| Ashkenazi Jewishnot grpmax-eligible | 0.304% | 329 |
| Remaining individualsnot grpmax-eligible | 0.16% | 625 |
| European (non-Finnish) | 0.131% | 763 |
| African / African-American | 0.0346% | 2,887 |
| Admixed American | 0.025% | 4,001 |
| Finnishnot grpmax-eligible | 0.00937% | 10,670 |
| South Asian | 0.00769% | 13,012 |
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
- CFAP251
- Protein
- p.Ile453=
- Coding
- c.1359C>T
- MANE Select
- NM_144668
- dbSNP
- rs61952863
- Type
- single nucleotide variant
- Location
- chr12:121954158 (GRCh38)
- Gene constraint
- LOEUF 0.829 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 76.84 · 1 PDB
- Residue 453
- a UniProt-annotated variant site (in spgf33)
Similar variants
- CFAP251 p.Ile453Val Likely benign ★ same residue
- CFAP251 p.Arg267Ter Pathogenic ★★ same type
- CFAP251 p.Glu111Ter Pathogenic/Likely pathogenic ★★ same type
- CFAP251 c.-20-20T>C Benign ★★ same type
- CFAP251 p.Arg417Gln Benign ★★ same type
- CFAP251 p.Ile970= Likely benign ★★ same type
- CFAP251 p.Val307Ile Benign ★★ ⚠ same type
- CFAP251 c.-20-2A>C Likely pathogenic ★ same type
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/cfap251-p-ile453 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown