FA2H p.Leu85=
c.255C>T · VCV4931255
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0174%, mid)
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 -0.071 | GERP -2.1, phastCons 0.65 |
| Overall | ||
| CADD | 8.507 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0174%
Middle Eastern · 1/5,748 alleles
Filtering AF
2.9e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000259%
4/1,542,644 alleles · ultra-rare
exomes 4/1,390,370 · genomes 0/152,274 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0174% | 5,748 |
| Remaining individualsnot grpmax-eligible | 0.00167% | 59,740 |
| European (non-Finnish) | 0.000173% | 576,668 |
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.Leu85=
- Coding
- c.255C>T
- MANE Select
- NM_024306
- Type
- single nucleotide variant
- Location
- chr16:74774501 (GRCh38)
- Gene constraint
- LOEUF 0.759 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 85.53
- Residue 85
- the cytochrome b5 heme-binding domain
Similar variants
- FA2H c.363+2T>C Pathogenic/Likely pathogenic ★★ same type
- FA2H c.506+1G>C Pathogenic/Likely pathogenic ★★ same type
- FA2H c.786+1G>A Pathogenic/Likely pathogenic ★★ same type
- FA2H p.Arg127Ter Pathogenic/Likely pathogenic ★★ same type
- FA2H p.Arg189Ter Pathogenic ★★ same type
- FA2H p.Arg197Ter Pathogenic/Likely pathogenic ★★ same type
- FA2H p.Arg235His Pathogenic/Likely pathogenic ★★ same type
- FA2H p.Arg269His Pathogenic/Likely pathogenic ★★ same type
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-leu85 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown