IGFALS p.Ala218=
c.654C>T · VCV4927385
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0342%, mid)
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 -6.8 | GERP -5.1 |
| Overall | ||
| CADD | 0.772 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0342%
Middle Eastern · 2/5,852 alleles
Filtering AF
0.00903%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00717%
Overall
0.00484%
75/1,549,364 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0342% | 2,926 |
| South Asian | 0.0153% | 6,520 |
| Remaining individualsnot grpmax-eligible | 0.00664% | 15,070 |
| European (non-Finnish) | 0.0046% | 21,722 |
| Admixed American | 0.00385% | 25,972 |
| East Asian | 0.00242% | 41,322 |
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
- IGFALS
- Protein
- p.Ala218=
- Coding
- c.654C>T
- MANE Select
- NM_004970
- Type
- single nucleotide variant
- Location
- chr16:1791764 (GRCh38)
- Gene constraint
- LOEUF 1.908 · pLI 0.07 (gnomAD)
- Structure
- AlphaFold pLDDT 91.13 · 1 PDB
Similar variants
- IGFALS p.Asn276Ser Likely pathogenic ★★ same type
- IGFALS p.Ala147Thr Uncertain significance ★★ ⚠ same type
- IGFALS p.Ala229Thr Uncertain significance ★★ ⚠ same type
- IGFALS p.Ala258Val Uncertain significance ★★ ⚠ same type
- IGFALS p.Ala551Thr Uncertain significance ★★ ⚠ same type
- IGFALS p.Arg157His Uncertain significance ★★ ⚠ same type
- IGFALS p.Arg306Gln Uncertain significance ★★ ⚠ same type
- IGFALS p.Arg308His 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/igfals-p-ala218 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown