ACSL4 p.Pro404=
c.1212G>A · rs370509273 · VCV434073
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0459%, mid)
Conditions
1
Inborn genetic diseases
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 -20 | GERP -3.6 |
| Overall | ||
| CADD | 0.056 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0459%
Middle Eastern · 2/4,362 alleles
Filtering AF
0.00811%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0034%
Overall
0.0053%
64/1,208,113 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0459% | 2,181 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0364% | 2,749 |
| Remaining individualsnot grpmax-eligible | 0.0147% | 6,790 |
| Admixed American | 0.0109% | 9,136 |
| East Asian | 0.00889% | 11,253 |
| European (non-Finnish) | 0.00425% | 23,526 |
| African / African-American | 0.00175% | 57,046 |
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
- ACSL4
- Protein
- p.Pro404=
- Coding
- c.1212G>A
- MANE Select
- NM_001318510
- dbSNP
- rs370509273
- Type
- single nucleotide variant
- Location
- chrX:109668204 (GRCh38)
- Structure
- AlphaFold pLDDT 90.46
Similar variants
- ACSL4 p.Pro404Leu Uncertain significance ★★ ⚠ same residue
- ACSL4 p.Pro404Gln Uncertain significance ★ ⚠ same residue
- ACSL4 p.Asn95Asp Uncertain significance ★★ ⚠ same condition
- ACSL4 p.Asn95Ser Uncertain significance ★★ ⚠ same condition
- ACSL4 p.His23Arg Uncertain significance ★★ ⚠ same condition
- ACSL4 p.Ser501Tyr Uncertain significance ★★ ⚠ same condition
- ACSL4 p.Tyr132Cys Uncertain significance ★★ ⚠ same condition
- ACSL4 p.Asn153Ser Benign/Likely benign ★★ ⚠ 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/acsl4-p-pro404 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown