Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 28.5%, amr) — 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 -5.2 | GERP -5.5 |
| Overall | ||
| CADD | 0.043 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
28.5%
Admixed American · 17,092/59,980 alleles
Filtering AF
28.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 28%
Overall
11.5%
185,071/1,613,338 alleles · common
exomes 168,868/1,461,138 · genomes 16,203/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 28.5% | 4 |
| South Asian | 12.9% | 8 |
| Amishnot grpmax-eligible | 12% | 8 |
| European (non-Finnish) | 11.4% | 9 |
| Remaining individualsnot grpmax-eligible | 11.1% | 9 |
| Ashkenazi Jewishnot grpmax-eligible | 11% | 9 |
| Middle Eastern | 9.52% | 10 |
| African / African-American | 8.26% | 12 |
| Finnishnot grpmax-eligible | 7.14% | 14 |
| East Asian | 0.058% | 1,725 |
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.Thr2153=
- Coding
- c.6459T>C
- MANE Select
- NM_207361
- dbSNP
- rs9548507
- Type
- single nucleotide variant
- Location
- chr13:38850117 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
- Residue 2153
- the calx-beta 4 domain; a UniProt-annotated variant site (in cryptop); a UniProt-annotated variant site (in)
Similar variants
- FREM2 p.Thr2153Asn Uncertain significance ★ ⚠ same residue
- 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
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-thr2153 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown