Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 10 submitters
gnomAD v4.1
Common
common (popmax 81%, amr) — too common for a highly-penetrant pathogenic allele
Conditions
1
combined malonic and methylmalonic acidemia
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 -0.8 | GERP -3.6 |
| Overall | ||
| CADD | 5.005 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
81%
Admixed American · 48,519/59,920 alleles
Filtering AF
80.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 80.1%
Overall
75.4%
1,214,660/1,611,744 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 81% | 1 |
| European (non-Finnish) | 78.8% | 1 |
| Amishnot grpmax-eligible | 77.4% | 1 |
| Finnishnot grpmax-eligible | 76.1% | 1 |
| Remaining individualsnot grpmax-eligible | 73% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 72.3% | 1 |
| Middle Eastern | 72.3% | 1 |
| African / African-American | 61.1% | 2 |
| South Asian | 55.5% | 2 |
| East Asian | 46.8% | 2 |
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.Cys102=
- Coding
- c.306C>T
- MANE Select
- NM_001243279
- dbSNP
- rs6500526
- Type
- single nucleotide variant
- Location
- chr16:89100987 (GRCh38)
- Gene constraint
- LOEUF 1.715 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.58
Disease context
combined malonic and methylmalonic acidemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Combined malonic and methylmalonic acidemia (Orphanet):
- Inheritance
- Autosomal dominant, Autosomal recessive
- Onset
- All ages
- Prevalence
- 1-9 / 100 000 (United States)
Similar variants
- ACSF3 p.Cys102fs 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
- ACSF3 c.666+1G>T 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-cys102 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown