IFT74 p.Glu466=
c.1398A>G · VCV3357261
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00538%, amr)
Conditions
1
IFT74-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.3 | GERP -4.5, phastCons 1 |
| Overall | ||
| CADD | 4.566 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00538%
Admixed American · 3/55,780 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000696%
Overall
0.000251%
4/1,594,186 alleles · very rare
exomes 3/1,442,044 · genomes 1/152,142 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00538% | 18,593 |
| European (non-Finnish) | 8.53e-05% | 1,172,366 |
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
- IFT74
- Protein
- p.Glu466=
- Coding
- c.1398A>G
- MANE Select
- NM_025103
- Type
- single nucleotide variant
- Location
- chr9:27055673 (GRCh38)
- Gene constraint
- LOEUF 1.508 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.21
- Residue 466
- a UniProt-annotated variant site (in jbts40)
Disease context
IFT74-related disorder
Similar variants
- IFT74 p.Glu466Asp Uncertain significance ★★ ⚠ same residue
- IFT74 p.Glu466Lys Uncertain significance ★★ ⚠ same residue
- IFT74 c.1685-1G>T Pathogenic/Likely pathogenic ★★ same condition
- IFT74 p.Thr327Lys Uncertain significance ★★ ⚠ same condition
- IFT74 p.Gln342Ter Conflicting classifications of pathogenicity ★ same condition
- IFT74 p.Arg288Ter Likely pathogenic same condition
- IFT74 c.1054+7363T>C Uncertain significance same condition
- IFT74 c.1054+7400A>C Uncertain significance 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/ift74-p-glu466 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown