FAR1 p.Ala359=
c.1077C>G · rs146816221 · VCV757666
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0833%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4 | GERP 0.16, phastCons 1 |
| Overall | ||
| CADD | 11.39 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0833%
European (non-Finnish) · 982/1,179,490 alleles
Filtering AF
0.0789%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0771%
Overall
0.0632%
1,020/1,612,902 alleles · ultra-rare
exomes 958/1,460,902 · genomes 62/152,000 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0833% | 1,201 |
| Remaining individualsnot grpmax-eligible | 0.0368% | 2,715 |
| African / African-American | 0.00936% | 10,682 |
| Finnishnot grpmax-eligible | 0.00781% | 12,798 |
| Admixed American | 0.00501% | 19,945 |
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
- FAR1
- Protein
- p.Ala359=
- Coding
- c.1077C>G
- MANE Select
- NM_032228
- dbSNP
- rs146816221
- Type
- single nucleotide variant
- Location
- chr11:13714630 (GRCh38)
- Gene constraint
- LOEUF 0.595 · pLI 0.57 (gnomAD)
- Structure
- AlphaFold pLDDT 94.13
- Residue 359
- a UniProt-annotated variant site (in pfcrd; results in a complete loss of enzyme activity)
Similar variants
- FAR1 p.Ala359Val Uncertain significance ★ ⚠ same residue
- FAR1 c.-7-2A>G Likely pathogenic ★★ same type
- FAR1 p.Arg480Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
- FAR1 p.Arg480His Pathogenic/Likely pathogenic ★★ same type
- FAR1 p.Arg480Leu Pathogenic ★★ same type
- FAR1 c.546-13A>G Uncertain significance ★★ same type
- FAR1 p.Ala361Val Uncertain significance ★★ ⚠ same type
- FAR1 p.Arg133Gln Uncertain significance ★★ ⚠ 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/far1-p-ala359 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown