FA2H p.Arg53=
c.159G>A · rs2544384425 · VCV2765287
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00122%, sas)
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 1.5 | GERP -0.56, phastCons 1 |
| Overall | ||
| CADD | 13.84 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00122%
South Asian · 1/82,004 alleles
Overall
6.55e-05%
1/1,527,430 alleles · very rare
exomes 1/1,375,140 · genomes 0/152,290 · 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
- FA2H
- Protein
- p.Arg53=
- Coding
- c.159G>A
- MANE Select
- NM_024306
- dbSNP
- rs2544384425
- Type
- single nucleotide variant
- Location
- chr16:74774597 (GRCh38)
- Gene constraint
- LOEUF 0.759 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.53
- Residue 53
- a UniProt-annotated variant site (in spg35; significantly reduced enzymatic function); the cytochrome b5 heme-binding domain
Similar variants
- FA2H p.Arg53_Ile58del Pathogenic ★★ same residue
- 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
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-arg53 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown