FREM2 p.Glu2202=
c.6606G>A · rs61749310 · VCV312010
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Common
common (popmax 5.97%, afr) — too common for a highly-penetrant pathogenic allele
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 0.85 | GERP -2.7, phastCons 0.99 |
| Overall | ||
| CADD | 2.728 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
5.97%
African / African-American · 4,474/74,998 alleles
Filtering AF
5.82%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.76%
Overall
0.317%
5,119/1,613,092 alleles · common
exomes 2,555/1,460,816 · genomes 2,564/152,276 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 5.97% | 17 |
| Admixed American | 0.433% | 231 |
| Remaining individualsnot grpmax-eligible | 0.417% | 240 |
| Middle Eastern | 0.368% | 272 |
| South Asian | 0.0319% | 3,139 |
| European (non-Finnish) | 0.00644% | 15,526 |
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.Glu2202=
- Coding
- c.6606G>A
- MANE Select
- NM_207361
- dbSNP
- rs61749310
- Type
- single nucleotide variant
- Location
- chr13:38850972 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
- Residue 2202
- 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-glu2202 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown