FARSA p.Ala378=
c.1134G>A · rs148613387 · VCV2649357
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0359%, 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 -3.3 | GERP -2.8 |
| Overall | ||
| CADD | 1.384 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0359%
European (non-Finnish) · 419/1,166,528 alleles
Filtering AF
0.033%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0319%
Overall
0.0279%
444/1,592,676 alleles · ultra-rare
exomes 397/1,440,482 · genomes 47/152,194 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0359% | 2,784 |
| Remaining individualsnot grpmax-eligible | 0.0114% | 8,782 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0107% | 9,370 |
| Admixed American | 0.00678% | 14,743 |
| African / African-American | 0.0067% | 14,931 |
| Finnishnot grpmax-eligible | 0.00632% | 15,820 |
| South Asian | 0.00227% | 44,082 |
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
- FARSA
- Protein
- p.Ala378=
- Coding
- c.1134G>A
- MANE Select
- NM_004461
- dbSNP
- rs148613387
- Type
- single nucleotide variant
- Location
- chr19:12924700 (GRCh38)
- Gene constraint
- LOEUF 0.784 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 88.43 · 3 PDB
- Residue 378
- a β-strand
Similar variants
- FARSA p.Pro347Leu Likely pathogenic ★★ same type
- FARSA p.Arg338Cys Uncertain significance ★★ ⚠ same type
- FARSA p.Gly306Ser Uncertain significance ★★ ⚠ same type
- FARSA c.1027-17T>C Benign ★★ same type
- FARSA p.Arg271His Pathogenic ★ same type
- FARSA p.Phe256Leu Pathogenic ★ same type
- FARSA p.Ala148Thr Uncertain significance ★ ⚠ same type
- FARSA p.Ala283Val 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/farsa-p-ala378 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown