FA2H p.Val177=
c.531G>A · rs775888031 · VCV1136673
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0107%, 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 -0.29 | GERP -4.2, phastCons 0.081 |
| Overall | ||
| CADD | 4.163 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0107%
African / African-American · 8/74,906 alleles
Filtering AF
0.00571%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00525%
Overall
0.00564%
91/1,613,674 alleles · ultra-rare
exomes 87/1,461,540 · genomes 4/152,134 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0107% | 9,363 |
| European (non-Finnish) | 0.00695% | 14,388 |
| Admixed American | 0.00167% | 59,986 |
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.Val177=
- Coding
- c.531G>A
- MANE Select
- NM_024306
- dbSNP
- rs775888031
- Type
- single nucleotide variant
- Location
- chr16:74726307 (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.Val177Met Conflicting classifications of pathogenicity ★ ⚠ 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-val177 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown