FH p.Ser366Arg
c.1096A>C · VCV4871334
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9995 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
hereditary neoplastic syndrome
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9995 | likely pathogenic ✓ concordant with ClinVar · top 1% in FH |
|---|---|---|
| REVEL | 0.91 | moderately pathogenic-leaning |
| SaProt | LLR -14.58 | 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 7.9 | GERP 2.8, phastCons 1 |
| Regional constraint | o/e 0.75 | unconstrained · MANE · 16 kb · p 7.5e-09 · regional, not allelic |
| Overall | ||
| CADD | 31.0 | 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
- FH
- Protein
- p.Ser366Arg
- Coding
- c.1096A>C
- MANE Select
- NM_000143
- Type
- single nucleotide variant
- Location
- chr1:241504054 (GRCh38)
- Gene constraint
- LOEUF 0.599 · pLI 0.27 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 92.92 · 8 PDB
- Residue 366
- a modified residue (phosphoserine); a binding site; a β-strand
Similar variants
- FH p.Ser366Asn Pathogenic/Likely pathogenic ★★ same residue
- FH p.Ser366= Likely benign ★★ same residue
- FH c.1108+1G>T Pathogenic/Likely pathogenic ★★ same condition
- FH c.1236+1G>A Pathogenic/Likely pathogenic ★★ same condition
- FH c.1236+1G>C Pathogenic ★★ same condition
- FH c.1236+2T>G Pathogenic ★★ same condition
- FH c.1237-1G>T Likely pathogenic ★★ same condition
- FH c.1390+1G>T Pathogenic/Likely pathogenic ★★ same condition
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/fh-p-ser366arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown