ACTG2 p.Glu242Lys
c.724G>A · VCV4795842
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.992 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
3/3 damaging
AlphaMissense, REVEL, SaProt
Conditions
1
megacystis-microcolon-intestinal hypoperistalsis syndrome 5
Computational evidence
| Protein change | ||
| AlphaMissense | 0.992 | likely pathogenic |
|---|---|---|
| REVEL | 0.885 | moderately pathogenic-leaning |
| SaProt | LLR -14.25 | damaging |
| ⇒ AlphaMissense, REVEL and SaProt all call this damaging. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.3, phastCons 1 |
| Regional constraint | o/e 0.48 | unconstrained · MANE · 18 kb · p 3.5e-30 · regional, not allelic |
| Overall | ||
| CADD | 31.0 | 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
- ACTG2
- Protein
- p.Glu242Lys
- Coding
- c.724G>A
- MANE Select
- NM_001615
- Type
- single nucleotide variant
- Location
- chr2:73914790 (GRCh38)
- Gene constraint
- LOEUF 0.626 · pLI 0.28 (gnomAD)
- Structure
- AlphaFold pLDDT 95.46 · 4 PDB
- Residue 242
- a β-strand
Similar variants
- ACTG2 p.Arg178Cys Pathogenic ★★ same condition
- ACTG2 p.Arg178His Pathogenic ★★ same condition
- ACTG2 p.Arg178Leu Pathogenic ★★ same condition
- ACTG2 p.Arg257Cys Pathogenic ★★ same condition
- ACTG2 p.Arg257His Pathogenic ★★ same condition
- ACTG2 p.Arg40Cys Pathogenic/Likely pathogenic ★★ same condition
- ACTG2 p.Arg40His Pathogenic/Likely pathogenic ★★ same condition
- ACTG2 p.Arg63Leu Likely pathogenic ★★ 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/actg2-p-glu242lys (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown