MACF1 p.Glu1018=
c.3054A>G · rs138972929 · VCV2074626
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.248%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.065 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.023 | GERP -3.5, phastCons 0.26 |
| Overall | ||
| CADD | 6.29 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.248%
African / African-American · 186/75,042 alleles
Filtering AF
0.219%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.207%
Overall
0.0141%
228/1,614,152 alleles · rare
exomes 130/1,461,876 · genomes 98/152,276 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.248% | 403 |
| Remaining individualsnot grpmax-eligible | 0.0288% | 3,473 |
| Admixed American | 0.0283% | 3,530 |
| Middle Eastern | 0.0165% | 6,060 |
| South Asian | 0.00329% | 30,361 |
| European (non-Finnish) | 0.000254% | 393,334 |
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
- MACF1
- Protein
- p.Glu1018=
- Coding
- c.3054A>G
- MANE Select
- NM_001394062
- dbSNP
- rs138972929
- Type
- single nucleotide variant
- Location
- chr1:39310382 (GRCh38)
- Gene constraint
- LOEUF 0.238 · pLI 1.00 (gnomAD)
- Residue 1018
- the 'disordered' region
Similar variants
- MACF1 p.Arg7251Pro Likely pathogenic ★★ same type
- MACF1 p.Ala5598Ser Uncertain significance ★★ same type
- MACF1 p.Ala601Pro Uncertain significance ★★ ⚠ same type
- MACF1 p.Arg1196Gln Uncertain significance ★★ ⚠ same type
- MACF1 p.Arg30Gln Uncertain significance ★★ same type
- MACF1 p.Arg3713Cys Uncertain significance ★★ ⚠ same type
- MACF1 p.Arg4674Cys Uncertain significance ★★ same type
- MACF1 p.Arg5490Gln 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/macf1-p-glu1018 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown