IGFALS p.His491=
c.1473C>T · VCV3768311
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000764%, nfe)
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 6.4 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 4.254 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000764%
European (non-Finnish) · 9/1,177,928 alleles
Filtering AF
0.00036%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00026%
Overall
0.000564%
9/1,594,920 alleles · very rare
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.His491=
- Coding
- c.1473C>T
- MANE Select
- NM_004970
- Type
- single nucleotide variant
- Location
- chr16:1790945 (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-his491 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown