FAS p.Ile233=
c.699C>A · VCV4874415
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.02 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.49 | GERP -2.7, phastCons 0.067 |
| Overall | ||
| CADD | 2.108 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/91,010 alleles
Overall
6.2e-05%
1/1,613,608 alleles · very rare
exomes 1/1,461,360 · genomes 0/152,248 · joint denominator
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
- FAS
- Protein
- p.Ile233=
- Coding
- c.699C>A
- MANE Select
- NM_000043
- Type
- single nucleotide variant
- Location
- chr10:89014141 (GRCh38)
- Gene constraint
- LOEUF 0.372 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.21 · 7 PDB
- Residue 233
- the 'interaction with calm' region; the death domain; the 'interaction with hipk3' region; an α-helix
Similar variants
- FAS p.Ile233Thr Uncertain significance ★★ ⚠ same residue
- FAS c.196+1G>A Pathogenic/Likely pathogenic ★★ same type
- FAS c.443+1G>A Pathogenic/Likely pathogenic ★★ same type
- FAS c.651+1G>A Pathogenic/Likely pathogenic ★★ same type
- FAS c.651+2T>C Pathogenic ★★ same type
- FAS p.Arg250Gln Pathogenic/Likely pathogenic ★★ same type
- FAS p.Arg250Gly Likely pathogenic ★★ same type
- FAS p.Arg250Ter Pathogenic/Likely pathogenic ★★ 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/fas-p-ile233 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown