FAS p.Gln196Ter
c.586C>T · VCV3765194
Pathogenic
Multiple submitters
Classification
Pathogenic
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 7 of 9 |
| Splicing | ||
| SpliceAI | Δ0.21 | acceptor loss, 17 bp away · masked 0 · deltas |
| Pangolin | Δ0.23 | loss · gain 0.00 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 0.14 | GERP -1.2, phastCons 0.001 |
| Overall | ||
| CADD | 26.6 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
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.Gln196Ter
- Coding
- c.586C>T
- MANE Select
- NM_000043
- Type
- single nucleotide variant
- Location
- chr10:89012016 (GRCh38)
- Gene constraint
- LOEUF 0.372 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.21 · 7 PDB
Similar variants
- FAS p.Gln196Glu Uncertain significance ★ ⚠ same residue
- FAS p.Gln196= Likely benign ★ 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-gln196ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown