IGFALS p.Pro523=
c.1569G>A · rs760061243 · VCV723901
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0677%, 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 -14 | GERP -4.7 |
| Overall | ||
| CADD | 0.098 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0677%
Middle Eastern · 4/5,912 alleles
Filtering AF
0.023%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0139%
Overall
0.00255%
40/1,565,974 alleles · ultra-rare
exomes 36/1,413,794 · genomes 4/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0677% | 1,478 |
| East Asian | 0.00714% | 13,997 |
| Admixed American | 0.0038% | 26,306 |
| European (non-Finnish) | 0.00251% | 39,883 |
| Remaining individualsnot grpmax-eligible | 0.00165% | 60,694 |
| African / African-American | 0.00136% | 73,748 |
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.Pro523=
- Coding
- c.1569G>A
- MANE Select
- NM_004970
- dbSNP
- rs760061243
- Type
- single nucleotide variant
- Location
- chr16:1790849 (GRCh38)
- Gene constraint
- LOEUF 1.908 · pLI 0.07 (gnomAD)
- Structure
- AlphaFold pLDDT 91.13 · 1 PDB
Similar variants
- IGFALS p.Pro523Leu Uncertain significance ★ ⚠ same residue
- 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
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-pro523 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown