FRMPD4 p.Pro74=
c.222G>A · rs779251615 · VCV1337349
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.15%, sas)
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 -5.6 | GERP -3.7 |
| Overall | ||
| CADD | 0.224 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.15%
South Asian · 85/56,663 alleles
Filtering AF
0.124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.115%
Overall
0.0125%
151/1,206,761 alleles · rare
exomes 147/1,094,992 · genomes 4/111,769 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.15% | 667 |
| Remaining individualsnot grpmax-eligible | 0.0147% | 6,788 |
| European (non-Finnish) | 0.00661% | 15,124 |
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.Pro74=
- Coding
- c.222G>A
- MANE Select
- NM_001368397
- dbSNP
- rs779251615
- Type
- single nucleotide variant
- Location
- chrX:12609784 (GRCh38)
- Structure
- AlphaFold pLDDT 54.86 · 5 PDB
Similar variants
- FRMPD4 p.Pro74Leu Likely benign ★ 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-pro74 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown