FRMPD4 p.Pro396=
c.1188G>A · VCV3363993
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00502%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.82 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.65 | gain · loss 0.29 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP -0.2 | GERP -2.6, phastCons 0.082 |
| Overall | ||
| CADD | 20.0 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00502%
Admixed American · 2/39,850 alleles
Filtering AF
0.000832%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000311%
Overall
0.000344%
4/1,163,920 alleles · very rare
exomes 2/1,051,379 · genomes 2/112,541 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00502% | 19,925 |
| European (non-Finnish) | 0.000231% | 433,678 |
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
- FRMPD4
- Protein
- p.Pro396=
- Coding
- c.1188G>A
- MANE Select
- NM_001368397
- Type
- single nucleotide variant
- Location
- chrX:12704476 (GRCh38)
- Structure
- AlphaFold pLDDT 54.86 · 5 PDB
- Residue 396
- the ferm domain
Similar variants
- FRMPD4 p.Pro396Leu Uncertain significance ★ ⚠ same residue
- FRMPD4 p.Ala1297Pro Uncertain significance ★★ ⚠ same type
- FRMPD4 p.Ala728Pro Uncertain significance ★★ ⚠ same type
- FRMPD4 p.Ala728Val Uncertain significance ★★ ⚠ same type
- FRMPD4 p.Ala809Thr Uncertain significance ★★ ⚠ same type
- FRMPD4 p.Arg1288Gln Uncertain significance ★★ ⚠ same type
- FRMPD4 p.Arg422Cys Uncertain significance ★★ ⚠ same type
- FRMPD4 p.Asn1270Ile Uncertain significance ★★ ⚠ 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/frmpd4-p-pro396 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown