FREM2 p.Asp2126=
c.6378T>C · VCV3576154
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00267%, afr)
Conditions
2
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 -2.6 | GERP -4.9 |
| Overall | ||
| CADD | 1.062 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00267%
African / African-American · 2/74,812 alleles
Filtering AF
0.000444%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000166%
Overall
0.000311%
5/1,608,588 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00267% | 37,406 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,276 |
| European (non-Finnish) | 0.00017% | 587,686 |
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.Asp2126=
- Coding
- c.6378T>C
- MANE Select
- NM_207361
- Type
- single nucleotide variant
- Location
- chr13:38848669 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
- Residue 2126
- the calx-beta 4 domain; a UniProt-annotated variant site (in cryptop)
Similar variants
- FREM2 p.Asp2126Asn 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-asp2126 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown