MACF1 p.Lys6700=
c.20100G>A · rs373353949 · VCV2075442
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0352%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.396 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 3.1 | GERP -0.5, phastCons 1 |
| Overall | ||
| CADD | 4.484 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0352%
Middle Eastern · 2/5,688 alleles
Filtering AF
0.00762%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00712%
Overall
0.00741%
113/1,525,992 alleles · ultra-rare
exomes 105/1,373,900 · genomes 8/152,092 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0352% | 2,844 |
| European (non-Finnish) | 0.00908% | 11,009 |
| Remaining individualsnot grpmax-eligible | 0.00517% | 19,349 |
| Admixed American | 0.00406% | 24,649 |
| South Asian | 0.00263% | 38,008 |
| African / African-American | 0.0014% | 71,364 |
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.Lys6700=
- Coding
- c.20100G>A
- MANE Select
- NM_001394062
- dbSNP
- rs373353949
- Type
- single nucleotide variant
- Location
- chr1:39448605 (GRCh38)
- Gene constraint
- LOEUF 0.238 · pLI 1.00 (gnomAD)
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-lys6700 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown