Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Common
common (popmax 17%, afr) — too common for a highly-penetrant pathogenic allele
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 -3.7 | GERP -5.2 |
| Overall | ||
| CADD | 5.871 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
17%
African / African-American · 12,709/74,826 alleles
Filtering AF
16.7%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 16.6%
Overall
0.956%
15,374/1,607,388 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 17% | 6 |
| Remaining individualsnot grpmax-eligible | 1.33% | 75 |
| Admixed American | 1.29% | 78 |
| Ashkenazi Jewishnot grpmax-eligible | 0.969% | 103 |
| Middle Eastern | 0.929% | 108 |
| European (non-Finnish) | 0.0583% | 1,715 |
| South Asian | 0.0431% | 2,320 |
| Finnishnot grpmax-eligible | 0.00319% | 31,367 |
| East Asian | 0.00224% | 44,726 |
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.Pro101=
- Coding
- c.303C>A
- MANE Select
- NM_207361
- dbSNP
- rs8002488
- Type
- single nucleotide variant
- Location
- chr13:38687647 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
Similar variants
- 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
- FREM2 p.Gln717Ter Likely pathogenic ★★ same condition
- FREM2 p.Ala1659Thr Uncertain significance ★★ ⚠ same condition
- FREM2 p.Ala1664Val Uncertain significance ★★ ⚠ 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-pro101 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown