FA2H p.Pro148=
c.444G>T · rs138087787 · VCV696472
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.133%, 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 -14 | GERP -3.9 |
| Overall | ||
| CADD | 0.697 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.133%
African / African-American · 100/75,052 alleles
Filtering AF
0.112%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.104%
Overall
0.00681%
110/1,614,132 alleles · rare
exomes 51/1,461,808 · genomes 59/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.133% | 751 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,927 |
| Admixed American | 0.00167% | 60,026 |
| European (non-Finnish) | 0.000169% | 590,009 |
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.Pro148=
- Coding
- c.444G>T
- MANE Select
- NM_024306
- dbSNP
- rs138087787
- Type
- single nucleotide variant
- Location
- chr16:74727306 (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 p.Pro148Leu Pathogenic/Likely pathogenic ★★ same residue
- FA2H p.Pro148Thr Uncertain significance ★ ⚠ 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
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-pro148 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown