FAS p.Cys82Arg
c.244T>C · VCV4083279
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.8614 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.8614 | likely pathogenic ✓ concordant with ClinVar · top 7% in FAS |
|---|---|---|
| REVEL | 0.845 | moderately pathogenic-leaning |
| SaProt | LLR -13.72 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.4 | GERP 1.6, phastCons 1 |
| Regional constraint | o/e 0.92 | unconstrained · MANE · 23 kb · p 0.16 · regional, not allelic |
| Overall | ||
| CADD | 24.6 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- FAS
- Protein
- p.Cys82Arg
- Coding
- c.244T>C
- MANE Select
- NM_000043
- Type
- single nucleotide variant
- Location
- chr10:89007747 (GRCh38)
- Gene constraint
- LOEUF 0.372 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.21 · 7 PDB
- Residue 82
- a disulfide bond; a UniProt-annotated variant site (in alps1a); a β-strand
Similar variants
- FAS p.Cys82= Likely benign ★★ same residue
- FAS p.Cys82Tyr 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
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-cys82arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown