FREM2 p.Pro2113=
c.6339C>T · rs116383837 · VCV312007
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.06%, 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 3.3 | GERP 0.71, phastCons 1 |
| Overall | ||
| CADD | 10.17 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.06%
African / African-American · 2,292/74,998 alleles
Filtering AF
2.95%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.91%
Overall
0.167%
2,688/1,613,890 alleles · low-frequency
exomes 1,316/1,461,668 · genomes 1,372/152,222 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.06% | 33 |
| Admixed American | 0.288% | 347 |
| Remaining individualsnot grpmax-eligible | 0.237% | 422 |
| Middle Eastern | 0.215% | 466 |
| South Asian | 0.00769% | 13,011 |
| European (non-Finnish) | 0.00466% | 21,453 |
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.Pro2113=
- Coding
- c.6339C>T
- MANE Select
- NM_207361
- dbSNP
- rs116383837
- Type
- single nucleotide variant
- Location
- chr13:38848630 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
- Residue 2113
- a UniProt-annotated variant site (in cryptop)
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-pro2113 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown