MACF1 p.Pro918=
c.2754C>G · rs139266313 · VCV2712840
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.143%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.277 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -6.2 | GERP -4 |
| Overall | ||
| CADD | 5.926 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.143%
African / African-American · 107/75,040 alleles
Filtering AF
0.121%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.112%
Overall
0.00743%
120/1,614,146 alleles · rare
exomes 43/1,461,814 · genomes 77/152,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.143% | 701 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,930 |
| Admixed American | 0.00833% | 12,007 |
| European (non-Finnish) | 8.47e-05% | 1,179,984 |
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.Pro918=
- Coding
- c.2754C>G
- MANE Select
- NM_001394062
- dbSNP
- rs139266313
- Type
- single nucleotide variant
- Location
- chr1:39303043 (GRCh38)
- Gene constraint
- LOEUF 0.238 · pLI 1.00 (gnomAD)
- Residue 918
- the sh3 domain
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-pro918 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown