MACF1 p.Leu769=
c.2307G>C · rs116026083 · VCV1607147
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.29%, afr)
Conditions
1
lissencephaly 9 with complex brainstem malformation
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.061 | GERP -4.1, phastCons 0.58 |
| Overall | ||
| CADD | 4.919 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.29%
African / African-American · 2,467/75,028 alleles
Filtering AF
3.18%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.14%
Overall
0.175%
2,825/1,614,142 alleles · low-frequency
exomes 1,353/1,461,830 · genomes 1,472/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.29% | 30 |
| Remaining individualsnot grpmax-eligible | 0.259% | 386 |
| Admixed American | 0.223% | 448 |
| Middle Eastern | 0.0825% | 1,212 |
| South Asian | 0.00878% | 11,386 |
| European (non-Finnish) | 0.00415% | 24,082 |
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.Leu769=
- Coding
- c.2307G>C
- MANE Select
- NM_001394062
- dbSNP
- rs116026083
- Type
- single nucleotide variant
- Location
- chr1:39295834 (GRCh38)
- Gene constraint
- LOEUF 0.238 · pLI 1.00 (gnomAD)
Similar variants
- MACF1 p.Arg7251Pro Likely pathogenic ★★ same condition
- MACF1 p.Arg30Gln Uncertain significance ★★ same condition
- MACF1 p.Arg3713Cys Uncertain significance ★★ ⚠ same condition
- MACF1 p.Arg6864Gln Uncertain significance ★★ same condition
- MACF1 p.Arg7005Trp Uncertain significance ★★ ⚠ same condition
- MACF1 p.Glu6915Lys Uncertain significance ★★ same condition
- MACF1 p.Ile380Thr Uncertain significance ★★ ⚠ same condition
- MACF1 p.Leu6865Phe Uncertain significance ★★ ⚠ 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/macf1-p-leu769 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown