MACF1 p.Cys5546Phe
c.16637G>T · rs575642095 · VCV2405221
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.128%, sas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.057 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.5 | GERP 0.018, phastCons 1 |
| Regional constraint | o/e 0.87 | unconstrained · MANE · 93 kb · p 4.8e-14 · regional, not allelic |
| Overall | ||
| CADD | 17.57 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.128%
South Asian · 117/91,078 alleles
Filtering AF
0.11%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.102%
Overall
0.00904%
146/1,614,200 alleles · rare
exomes 136/1,461,892 · genomes 10/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.128% | 778 |
| Middle Eastern | 0.099% | 1,010 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,946 |
| European (non-Finnish) | 0.00119% | 84,289 |
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.Cys5546Phe
- Coding
- c.16637G>T
- MANE Select
- NM_001394062
- dbSNP
- rs575642095
- Type
- single nucleotide variant
- Location
- chr1:39428121 (GRCh38)
- Gene constraint
- LOEUF 0.238 · pLI 1.00 (gnomAD)
Similar variants
- MACF1 p.Ala5598Ser Uncertain significance ★★ same condition
- MACF1 p.Ala601Pro Uncertain significance ★★ ⚠ same condition
- MACF1 p.Arg30Gln Uncertain significance ★★ same condition
- MACF1 p.Arg3713Cys Uncertain significance ★★ ⚠ same condition
- MACF1 p.Arg4674Cys Uncertain significance ★★ same condition
- MACF1 p.Arg5490Gln Uncertain significance ★★ ⚠ same condition
- MACF1 p.Arg5875Cys Uncertain significance ★★ same condition
- MACF1 p.Arg6864Gln 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-cys5546phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown