FREM2 p.Phe2132=
c.6396C>T · rs61745902 · VCV702035
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.86%, afr)
Conditions
1
Fraser syndrome 2
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 1.8 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 7.659 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.86%
African / African-American · 1,394/75,004 alleles
Filtering AF
1.78%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.74%
Overall
0.0944%
1,524/1,613,716 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.86% | 54 |
| Remaining individualsnot grpmax-eligible | 0.0928% | 1,077 |
| Admixed American | 0.0783% | 1,277 |
| Middle Eastern | 0.033% | 3,030 |
| South Asian | 0.00769% | 13,008 |
| European (non-Finnish) | 0.00136% | 73,734 |
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.Phe2132=
- Coding
- c.6396C>T
- MANE Select
- NM_207361
- dbSNP
- rs61745902
- Type
- single nucleotide variant
- Location
- chr13:38850054 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
- Residue 2132
- the calx-beta 4 domain; a UniProt-annotated variant site (in cryptop)
Similar variants
- FREM2 p.Arg1355Ter Pathogenic/Likely pathogenic ★★ same condition
- FREM2 p.Arg638Ter Likely pathogenic ★★ same condition
- FREM2 p.Arg736Ter Pathogenic ★★ same condition
- FREM2 p.Arg809Ter Pathogenic ★★ same condition
- FREM2 p.Gln1051Ter Pathogenic/Likely pathogenic ★★ same condition
- FREM2 p.Gln717Ter Likely pathogenic ★★ same condition
- FREM2 p.Ala1659Thr Uncertain significance ★★ ⚠ same condition
- FREM2 p.Ala1664Val Uncertain significance ★★ ⚠ same condition
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-phe2132 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown