FREM2 p.Pro2817=
c.8451A>C · rs201533042 · VCV881199
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0039%, nfe)
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 -11 | GERP -5 |
| Overall | ||
| CADD | 0.004 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0039%
European (non-Finnish) · 46/1,179,970 alleles
Filtering AF
0.00299%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00267%
Overall
0.00297%
48/1,614,092 alleles · very rare
exomes 45/1,461,816 · genomes 3/152,276 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0039% | 25,652 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
| African / African-American | 0.00133% | 75,034 |
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.Pro2817=
- Coding
- c.8451A>C
- MANE Select
- NM_207361
- dbSNP
- rs201533042
- Type
- single nucleotide variant
- Location
- chr13:38876289 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
- Residue 2817
- 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-pro2817 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown