AFG2A p.Glu430=
c.1290G>A · rs1729067022 · VCV1087764
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000255%, nfe)
Conditions
1
microcephaly-intellectual disability-sensorineural hearing loss-epilepsy-abnormal muscle tone syndrome
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 1.2 | GERP -1.7, phastCons 1 |
| Overall | ||
| CADD | 5.919 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000255%
European (non-Finnish) · 3/1,175,020 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000207%
3/1,451,532 alleles · very rare
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
- AFG2A
- Protein
- p.Glu430=
- Coding
- c.1290G>A
- MANE Select
- NM_145207
- dbSNP
- rs1729067022
- Type
- single nucleotide variant
- Location
- chr4:122936112 (GRCh38)
- Structure
- AlphaFold pLDDT 73.21 · 2 PDB
- Residue 430
- a UniProt-annotated variant site (in nedhsb)
Similar variants
- AFG2A c.1714+1G>A Pathogenic ★★ same condition
- AFG2A c.446+1G>A Likely pathogenic ★★ same condition
- AFG2A p.Ala844Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
- AFG2A p.Arg445Ter Pathogenic/Likely pathogenic ★★ same condition
- AFG2A p.Arg510Ter Pathogenic/Likely pathogenic ★★ same condition
- AFG2A p.Arg514Ter Pathogenic/Likely pathogenic ★★ same condition
- AFG2A p.Arg538Ter Pathogenic/Likely pathogenic ★★ same condition
- AFG2A p.Arg655Ter Pathogenic/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/afg2a-p-glu430 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown