ACTC1 p.Ile36Leu
c.106A>C · VCV3754757
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
ambiguous
0.5094 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/2 damaging
REVEL, SaProt · AlphaMissense no call
Conditions
3
atrial septal defect 5
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5094 | ambiguous |
|---|---|---|
| REVEL | 0.729 | pathogenic-leaning |
| SaProt | LLR -12.73 | damaging |
| ⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 6.2 | GERP 2.3, phastCons 1 |
| Regional constraint | o/e 0.34 | constrained · MANE · 1,330 bp · p 2.8e-11 · regional, not allelic |
| Overall | ||
| CADD | 28.2 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ACTC1
- Protein
- p.Ile36Leu
- Coding
- c.106A>C
- MANE Select
- NM_005159
- Type
- single nucleotide variant
- Location
- chr15:34794703 (GRCh38)
- Gene constraint
- LOEUF 0.511 · pLI 0.97 · ClinGen HI 1/3 (gnomAD)
- Structure
- AlphaFold pLDDT 95.47 · 16 PDB
Similar variants
- ACTC1 p.Ile36Met Uncertain significance ★★ ⚠ same residue
- ACTC1 p.Ile36= Likely benign ★★ same residue
- ACTC1 p.Glu101Lys Pathogenic ★★★ same condition
- ACTC1 p.Val56Ile Uncertain significance ★★★ ⚠ same condition
- ACTC1 p.Ala297Ser Pathogenic ★★ ⚠ same condition
- ACTC1 p.Gly247Asp Pathogenic/Likely pathogenic ★★ same condition
- ACTC1 p.Thr128Ile Likely pathogenic ★★ same condition
- ACTC1 c.455-6G>A 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/actc1-p-ile36leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown