IGFALS p.Leu271=
c.813G>C · rs369679075 · VCV734560
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.588%, amr)
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 -0.59 | GERP -1.1, phastCons 0.02 |
| Overall | ||
| CADD | 4.787 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.588%
Admixed American · 311/52,856 alleles
Filtering AF
0.535%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.513%
Overall
0.0212%
332/1,564,398 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.588% | 170 |
| Remaining individualsnot grpmax-eligible | 0.0214% | 4,664 |
| African / African-American | 0.0109% | 9,215 |
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.Leu271=
- Coding
- c.813G>C
- MANE Select
- NM_004970
- dbSNP
- rs369679075
- Type
- single nucleotide variant
- Location
- chr16:1791605 (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-leu271 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown