FRMD5 p.Pro339=
c.1017G>A · VCV3770474
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.44%, 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 -5.8 | GERP -4.3 |
| Overall | ||
| CADD | 7.517 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.44%
South Asian · 401/91,056 alleles
Filtering AF
0.405%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.395%
Overall
0.348%
5,618/1,613,914 alleles · rare
exomes 5,212/1,461,650 · genomes 406/152,264 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.44% | 227 |
| European (non-Finnish) | 0.408% | 245 |
| Ashkenazi Jewishnot grpmax-eligible | 0.331% | 302 |
| Remaining individualsnot grpmax-eligible | 0.205% | 488 |
| Admixed American | 0.17% | 588 |
| Finnishnot grpmax-eligible | 0.05% | 2,001 |
| African / African-American | 0.044% | 2,274 |
| Middle Eastern | 0.0165% | 6,062 |
| East Asian | 0.00891% | 11,222 |
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
- FRMD5
- Protein
- p.Pro339=
- Coding
- c.1017G>A
- MANE Select
- NM_032892
- Type
- single nucleotide variant
- Location
- chr15:43884738 (GRCh38)
- Gene constraint
- LOEUF 0.488 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 75.79
- Residue 339
- the 'interaction with rock1' region
Similar variants
- FRMD5 p.Arg553Thr Uncertain significance ★★ ⚠ same type
- FRMD5 p.Glu169Lys Uncertain significance ★★ ⚠ same type
- FRMD5 c.*732G>C Likely benign ★★ same type
- FRMD5 p.Pro426= Benign ★★ same type
- FRMD5 p.Thr181Met Benign/Likely benign ★★ same type
- FRMD5 c.1135+1G>A Pathogenic ★ same type
- FRMD5 p.Arg316Leu Likely pathogenic ★ same type
- FRMD5 p.Met346Thr 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/frmd5-p-pro339 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown