FA2H p.Ser186=
c.558C>G · VCV4725058
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Spastic paraplegia
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 4.6 | GERP -0.12, phastCons 1 |
| Overall | ||
| CADD | 9.252 | PHRED · no single calibrated threshold — expert panels disagree |
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
- FA2H
- Protein
- p.Ser186=
- Coding
- c.558C>G
- MANE Select
- NM_024306
- Type
- single nucleotide variant
- Location
- chr16:74726280 (GRCh38)
- Gene constraint
- LOEUF 0.759 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.53
Similar variants
- FA2H c.506+1G>C Pathogenic/Likely pathogenic ★★ same condition
- FA2H p.Arg269His Pathogenic/Likely pathogenic ★★ same condition
- FA2H p.Met1Val Pathogenic ★★ same condition
- FA2H p.Pro44Gln Pathogenic/Likely pathogenic ★★ same condition
- FA2H p.Pro44Ser Pathogenic/Likely pathogenic ★★ same condition
- FA2H p.Arg269Cys Uncertain significance ★★ ⚠ same condition
- FA2H p.Glu365Gln Uncertain significance ★★ ⚠ same condition
- FA2H p.Gly258Ser Uncertain significance ★★ ⚠ 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/fa2h-p-ser186 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown