FREM2 p.Arg1793=
c.5379T>C · rs757442342 · VCV2984396
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0147%, sas)
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 -1.4 | GERP -4.4 |
| Overall | ||
| CADD | 2.014 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0147%
South Asian · 13/88,504 alleles
Filtering AF
0.00867%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00689%
Overall
0.000945%
15/1,587,864 alleles · ultra-rare
exomes 13/1,435,612 · genomes 2/152,252 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0147% | 6,808 |
| African / African-American | 0.00269% | 37,178 |
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.Arg1793=
- Coding
- c.5379T>C
- MANE Select
- NM_207361
- dbSNP
- rs757442342
- Type
- single nucleotide variant
- Location
- chr13:38764419 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
- Residue 1793
- the calx-beta 1 domain; a UniProt-annotated variant site (in cryptop)
Similar variants
- FREM2 p.Arg1793Cys Uncertain significance ★★ same residue
- FREM2 p.Arg1793His Uncertain significance ★★ 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
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-arg1793 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown