MACF1 p.Arg2377fs
c.7129dup · rs766558667 · VCV2431958
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
ultra-rare (gnomAD MAF 1.342e-05)
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. | ||
| Consequence | frameshift | predicted loss-of-function in a LoF-intolerant gene |
|---|---|---|
| NMD | predicted | premature termination codon in exon 37 of 101 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.9, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
dbSNP / gnomAD
Global frequency
0.00134%
via dbSNP · ultra-rare
No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.
Variant & gene context
- Gene
- MACF1
- Protein
- p.Arg2377fs
- Coding
- c.7129dup
- MANE Select
- NM_001394062
- dbSNP
- rs766558667
- Type
- Duplication
- Location
- chr1:39333712 (GRCh38)
- Gene constraint
- LOEUF 0.238 · pLI 1.00 (gnomAD)
Similar variants
- MACF1 p.Glu110fs Likely pathogenic ★ same condition
- MACF1 p.Ala4556fs Uncertain significance ★ same condition
- 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.Glu5190del 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-arg2377fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown