ACSF3 p.Pro557=
c.1671G>A · rs747338200 · VCV1128235
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00195%, nfe)
Conditions
2
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 -11 | GERP -2.4 |
| Overall | ||
| CADD | 0.216 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00195%
European (non-Finnish) · 23/1,179,768 alleles
Filtering AF
0.0013%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00108%
Overall
0.00178%
26/1,461,182 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00195% | 51,294 |
| Admixed American | 0.00167% | 59,930 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,494 |
| South Asian | 0.0011% | 90,834 |
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
- ACSF3
- Protein
- p.Pro557=
- Coding
- c.1671G>A
- MANE Select
- NM_001243279
- dbSNP
- rs747338200
- Type
- single nucleotide variant
- Location
- chr16:89154147 (GRCh38)
- Gene constraint
- LOEUF 1.715 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.58
Similar variants
- ACSF3 p.Pro557Leu Uncertain significance ★★ ⚠ same residue
- ACSF3 p.Pro557fs Likely pathogenic ★ same residue
- ACSF3 c.1366+1G>A Likely pathogenic ★★ same condition
- ACSF3 c.1501+1G>A Likely pathogenic ★★ same condition
- ACSF3 c.1501+1G>T Likely pathogenic ★★ same condition
- ACSF3 c.1502-2A>G Pathogenic/Likely pathogenic ★★ same condition
- ACSF3 c.1613+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ACSF3 c.666+1G>A Pathogenic/Likely pathogenic ★★ 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/acsf3-p-pro557 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown