PEX7 p.Ala218=
c.654G>A · rs1414537422 · VCV594130
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0011%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.1 | GERP -3.8 |
| Overall | ||
| CADD | 3.527 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0011%
South Asian · 1/91,076 alleles
Overall
0.000124%
2/1,613,910 alleles · very rare
exomes 2/1,461,648 · genomes 0/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0011% | 91,076 |
| European (non-Finnish) | 8.48e-05% | 1,179,852 |
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
- PEX7
- Protein
- p.Ala218=
- Coding
- c.654G>A
- MANE Select
- NM_000288
- dbSNP
- rs1414537422
- Type
- single nucleotide variant
- Location
- chr6:136869910 (GRCh38)
- Gene constraint
- LOEUF 0.941 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.54
- Residue 218
- a UniProt-annotated variant site (in rcdp1)
Similar variants
- PEX7 p.Ala218Val Pathogenic/Likely pathogenic ★★ ⚠ same residue
- PEX7 p.Ala218fs Pathogenic ★ same residue
- PEX7 c.130+1G>A Pathogenic ★★ same type
- PEX7 c.131-1G>A Likely pathogenic ★★ same type
- PEX7 c.188+1G>A Pathogenic/Likely pathogenic ★★ same type
- PEX7 c.188+1G>C Pathogenic/Likely pathogenic ★★ same type
- PEX7 c.340-1G>T Likely pathogenic ★★ same type
- PEX7 c.634-2A>G Pathogenic/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/pex7-p-ala218 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown