IFT54 p.Lys581=
c.1743G>A · rs769447347 · VCV1907619
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00517%, nfe)
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 4.2 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 10.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00517%
European (non-Finnish) · 61/1,179,960 alleles
Filtering AF
0.0041%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00372%
Overall
0.00397%
64/1,613,016 alleles · very rare
exomes 59/1,460,816 · genomes 5/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00517% | 19,344 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,230 |
| Finnishnot grpmax-eligible | 0.00158% | 63,100 |
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
- IFT54
- Protein
- p.Lys581=
- Coding
- c.1743G>A
- MANE Select
- NM_015650
- dbSNP
- rs769447347
- Type
- single nucleotide variant
- Location
- chr2:238397512 (GRCh38)
- Structure
- AlphaFold pLDDT 61.95 · 2 PDB
- Residue 581
- the 'disc1-interaction domain' region
Similar variants
- IFT54 c.1159+1G>C Likely pathogenic ★★ same type
- IFT54 c.988-1G>A Likely pathogenic ★★ same type
- IFT54 c.988-1G>C Likely pathogenic ★★ same type
- IFT54 p.Arg565Ter Pathogenic/Likely pathogenic ★★ same type
- IFT54 p.Trp572Ter Pathogenic/Likely pathogenic ★★ same type
- IFT54 c.1452-5T>G Uncertain significance ★★ same type
- IFT54 c.1910+3G>T Uncertain significance ★★ same type
- IFT54 p.Ala513Val Uncertain significance ★★ ⚠ 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/ift54-p-lys581 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown