ACTG2 p.His74=
c.222C>T · rs149132468 · VCV3030932
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00933%, afr)
Conditions
1
ACTG2-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4 | GERP -5.6 |
| Overall | ||
| CADD | 11.17 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00933%
African / African-American · 7/75,022 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00308%
Overall
0.00167%
27/1,614,098 alleles · very rare
exomes 24/1,461,888 · genomes 3/152,210 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00933% | 10,717 |
| East Asian | 0.00891% | 11,220 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,253 |
| South Asian | 0.0022% | 45,538 |
| European (non-Finnish) | 0.00102% | 98,335 |
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
- ACTG2
- Protein
- p.His74=
- Coding
- c.222C>T
- MANE Select
- NM_001615
- dbSNP
- rs149132468
- Type
- single nucleotide variant
- Location
- chr2:73902455 (GRCh38)
- Gene constraint
- LOEUF 0.626 · pLI 0.28 (gnomAD)
- Structure
- AlphaFold pLDDT 95.46 · 4 PDB
- Residue 74
- a modified residue (tele-methylhistidine)
Disease context
ACTG2-related disorder
Similar variants
- ACTG2 p.His74Gln Uncertain significance ★ ⚠ same residue
- ACTG2 p.Arg257His Pathogenic ★★ same condition
- ACTG2 p.Met45Thr Pathogenic/Likely pathogenic ★★ same condition
- ACTG2 p.Thr195Ile Conflicting classifications of pathogenicity ★ ⚠ same condition
- ACTG2 c.613+8G>T Benign same condition
- ACTG2 p.Gly269Glu Pathogenic ★ same condition
- ACTG2 p.Ala205Thr Pathogenic ★★ same type
- ACTG2 p.Arg148Cys Likely pathogenic ★★ 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/actg2-p-his74 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown