FREM2 p.Ser2269=
c.6807G>A · rs752080876 · VCV502616
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
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 -7.5 | GERP -4.8 |
| Overall | ||
| CADD | 0.051 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/59,998 alleles
Filtering AF
0.00145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00123%
Overall
0.00205%
33/1,613,344 alleles · very rare
exomes 27/1,461,236 · genomes 6/152,108 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 19,999 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,232 |
| African / African-American | 0.00267% | 37,436 |
| East Asian | 0.00223% | 44,868 |
| European (non-Finnish) | 0.00212% | 47,178 |
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.Ser2269=
- Coding
- c.6807G>A
- MANE Select
- NM_207361
- dbSNP
- rs752080876
- Type
- single nucleotide variant
- Location
- chr13:38851750 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
- Residue 2269
- the calx-beta 5 domain; a UniProt-annotated variant site (in cryptop)
Similar variants
- FREM2 p.Ser2269Ter Pathogenic ★ 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-ser2269 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown