AFG2A p.Pro187=
c.561G>A · rs545967731 · VCV763019
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00891%, eas)
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 -4.8 | GERP -3.2 |
| Overall | ||
| CADD | 0.611 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00891%
East Asian · 4/44,888 alleles
Filtering AF
0.00298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0018%
Overall
0.000991%
16/1,614,044 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00891% | 11,222 |
| Admixed American | 0.005% | 20,001 |
| South Asian | 0.00329% | 30,354 |
| African / African-American | 0.00267% | 37,507 |
| European (non-Finnish) | 0.000339% | 294,992 |
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.Pro187=
- Coding
- c.561G>A
- MANE Select
- NM_145207
- dbSNP
- rs545967731
- Type
- single nucleotide variant
- Location
- chr4:122934152 (GRCh38)
- Structure
- AlphaFold pLDDT 73.21 · 2 PDB
- Residue 187
- the 'required for interaction with afg2b and cinp' region; a UniProt-annotated variant site (in nedhsb)
Similar variants
- AFG2A p.Pro187Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
- 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
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-pro187 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown