FREM2 p.Val918=
c.2754C>T · rs140353326 · VCV435264
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.159%, 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 2.4 | GERP -0.42, phastCons 1 |
| Overall | ||
| CADD | 8.349 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.159%
African / African-American · 119/75,032 alleles
Filtering AF
0.135%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.127%
Overall
0.00824%
133/1,614,076 alleles · rare
exomes 68/1,461,824 · genomes 65/152,252 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.159% | 631 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,930 |
| Admixed American | 0.00333% | 30,009 |
| European (non-Finnish) | 0.000424% | 236,004 |
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.Val918=
- Coding
- c.2754C>T
- MANE Select
- NM_207361
- dbSNP
- rs140353326
- Type
- single nucleotide variant
- Location
- chr13:38690098 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
- Residue 918
- a UniProt-annotated variant site (in cryptop)
Similar variants
- 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
- FREM2 p.Gln1051Ter Pathogenic/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-val918 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown