FA2H p.Pro7=
c.21C>A · rs918733475 · VCV1428218
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0754%, afr)
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 0.69 | GERP -2.2, phastCons 0.98 |
| Overall | ||
| CADD | 12.66 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0754%
African / African-American · 49/64,952 alleles
Filtering AF
0.0586%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0526%
Overall
0.00409%
54/1,321,142 alleles · ultra-rare
exomes 26/1,169,032 · genomes 28/152,110 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0754% | 1,326 |
| Admixed American | 0.00826% | 12,113 |
| Remaining individualsnot grpmax-eligible | 0.00402% | 24,896 |
| East Asian | 0.00314% | 31,854 |
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.Pro7=
- Coding
- c.21C>A
- MANE Select
- NM_024306
- dbSNP
- rs918733475
- Type
- single nucleotide variant
- Location
- chr16:74774735 (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-pro7 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown