FREM2 p.Arg2066=
c.6198T>C · rs2541486633 · VCV2860072
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
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 -4.9 | GERP -4.9 |
| Overall | ||
| CADD | 1.752 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- FREM2
- Protein
- p.Arg2066=
- Coding
- c.6198T>C
- MANE Select
- NM_207361
- dbSNP
- rs2541486633
- Type
- single nucleotide variant
- Location
- chr13:38848489 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
- Residue 2066
- the calx-beta 3 domain; a UniProt-annotated variant site (in cryptop); a UniProt-annotated variant site (in)
Similar variants
- FREM2 p.Arg2066His Uncertain significance ★★ ⚠ same residue
- FREM2 p.Arg2066Cys Benign/Likely benign ★★ same residue
- FREM2 p.Arg2066Gly Conflicting classifications of pathogenicity ★ ⚠ 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
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-arg2066 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown