FRMD5 p.Pro426=
c.1278T>C · rs61735012 · VCV714651
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 6.42%, afr) — too common for a highly-penetrant pathogenic allele
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 -7.8 | GERP -1.7 |
| Overall | ||
| CADD | 0.507 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.42%
African / African-American · 4,814/75,036 alleles
Filtering AF
6.26%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.2%
Overall
0.336%
5,416/1,614,184 alleles · common
exomes 2,640/1,461,872 · genomes 2,776/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 6.42% | 16 |
| Remaining individualsnot grpmax-eligible | 0.482% | 208 |
| Admixed American | 0.398% | 251 |
| Middle Eastern | 0.165% | 606 |
| South Asian | 0.0154% | 6,506 |
| European (non-Finnish) | 0.00322% | 31,053 |
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.Pro426=
- Coding
- c.1278T>C
- MANE Select
- NM_032892
- dbSNP
- rs61735012
- Type
- single nucleotide variant
- Location
- chr15:43874320 (GRCh38)
- Gene constraint
- LOEUF 0.488 · pLI 0.99 (gnomAD)
- Structure
- AlphaFold pLDDT 75.79
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.Pro339= Likely 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-pro426 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown