FREM2 p.Pro1704=
c.5112T>G · rs145894184 · VCV2193924
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0333%, afr)
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 -2 | GERP -4.9 |
| Overall | ||
| CADD | 4.36 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0333%
African / African-American · 25/75,036 alleles
Filtering AF
0.0231%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0197%
Overall
0.00248%
40/1,613,794 alleles · ultra-rare
exomes 22/1,461,508 · genomes 18/152,286 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0333% | 3,001 |
| Admixed American | 0.0167% | 6,002 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,625 |
| South Asian | 0.0011% | 91,078 |
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
- FREM2
- Protein
- p.Pro1704=
- Coding
- c.5112T>G
- MANE Select
- NM_207361
- dbSNP
- rs145894184
- Type
- single nucleotide variant
- Location
- chr13:38692456 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
- Residue 1704
- a UniProt-annotated variant site (in cryptop)
Similar variants
- FREM2 p.Pro1704Ser Uncertain significance ★ same residue
- FREM2 c.5263+1G>A Likely pathogenic ★★ same type
- FREM2 c.6925+1G>T Likely pathogenic ★★ same type
- FREM2 p.Arg1355Ter Pathogenic/Likely pathogenic ★★ same type
- FREM2 p.Arg2243Ter Pathogenic/Likely pathogenic ★★ same type
- FREM2 p.Arg638Ter Likely pathogenic ★★ same type
- FREM2 p.Arg736Ter Pathogenic ★★ same type
- FREM2 p.Arg809Ter 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/frem2-p-pro1704 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown