ACTL6B p.Phe147del
c.435CTT[2] · rs772520618 · VCV635103
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
1
developmental and epileptic encephalopathy, 76
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.1 | GERP 1.4, phastCons 0.002 |
| Overall | ||
| CADD | 20.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,978 alleles
Filtering AF
0.000803%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00065%
Overall
0.00112%
18/1,613,796 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,978 |
| European (non-Finnish) | 0.00136% | 73,748 |
| African / African-American | 0.00134% | 74,898 |
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
- ACTL6B
- Protein
- p.Phe147del
- Coding
- c.435CTT[2]
- MANE Select
- NM_016188
- dbSNP
- rs772520618
- Type
- Microsatellite
- Location
- chr7:100650062 (GRCh38)
- Gene constraint
- LOEUF 0.954 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 91.52
- Residue 147
- a UniProt-annotated variant site (in dee76); a UniProt-annotated variant site (in dee76; uncertain significance)
Similar variants
- ACTL6B p.Lys237del Uncertain significance ★ same condition
- ACTL6B p.Arg97Ter Likely pathogenic ★★ same condition
- ACTL6B p.Gln186Ter Pathogenic/Likely pathogenic ★★ same condition
- ACTL6B p.Gln278Ter Likely pathogenic ★★ same condition
- ACTL6B p.Gly349Ser Likely pathogenic ★★ same condition
- ACTL6B p.Gly50fs Pathogenic/Likely pathogenic ★★ same condition
- ACTL6B p.Trp247Ter Likely pathogenic ★★ same condition
- ACTL6B p.Glu297Lys 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/actl6b-p-phe147del (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown