FREM2 p.Arg488=
c.1464G>T · rs139525161 · VCV2122062
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
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 -0.03 | GERP -5.2, phastCons 0.2 |
| Overall | ||
| CADD | 4.624 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/75,046 alleles
Overall
6.2e-05%
1/1,613,970 alleles · very rare
exomes 1/1,461,670 · genomes 0/152,300 · joint denominator
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.Arg488=
- Coding
- c.1464G>T
- MANE Select
- NM_207361
- dbSNP
- rs139525161
- Type
- single nucleotide variant
- Location
- chr13:38688808 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
Similar variants
- FREM2 p.Arg488Gln Uncertain significance ★★ ⚠ same residue
- FREM2 p.Arg488Leu 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-arg488 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown