FREM2 p.Pro789=
c.2367G>A · rs140101984 · VCV193528
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
rare (popmax 0.293%, afr)
Conditions
1
Fraser syndrome 2
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 -3.5 | GERP -5.2 |
| Overall | ||
| CADD | 1.153 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.293%
African / African-American · 220/75,014 alleles
Filtering AF
0.261%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.249%
Overall
0.0164%
264/1,613,912 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.293% | 341 |
| Middle Eastern | 0.033% | 3,030 |
| Admixed American | 0.0183% | 5,454 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,681 |
| South Asian | 0.011% | 9,104 |
| European (non-Finnish) | 0.000848% | 117,994 |
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.Pro789=
- Coding
- c.2367G>A
- MANE Select
- NM_207361
- dbSNP
- rs140101984
- Type
- single nucleotide variant
- Location
- chr13:38689711 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
- Residue 789
- a UniProt-annotated variant site (in cryptop)
Similar variants
- FREM2 p.Pro789Arg Uncertain significance ★★ same residue
- FREM2 p.Pro789Leu Uncertain significance ★★ same residue
- FREM2 p.Pro789Gln Uncertain significance ★ same residue
- FREM2 p.Arg1355Ter Pathogenic/Likely pathogenic ★★ same condition
- FREM2 p.Arg638Ter Likely pathogenic ★★ same condition
- FREM2 p.Arg736Ter Pathogenic ★★ same condition
- FREM2 p.Arg809Ter Pathogenic ★★ same condition
- FREM2 p.Gln1051Ter Pathogenic/Likely pathogenic ★★ same condition
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-pro789 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown