FREM2 p.Ala1029=
c.3087G>A · rs561336798 · VCV1370074
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
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 -0.07 | GERP -5.2 |
| Overall | ||
| CADD | 4.829 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,062 alleles
Filtering AF
0.00514%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00375%
Overall
0.00496%
80/1,614,172 alleles · ultra-rare
exomes 71/1,461,880 · genomes 9/152,292 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,062 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0135% | 7,402 |
| South Asian | 0.00988% | 10,120 |
| Admixed American | 0.00667% | 15,004 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,626 |
| Finnishnot grpmax-eligible | 0.00625% | 16,009 |
| African / African-American | 0.00533% | 18,761 |
| European (non-Finnish) | 0.00424% | 23,601 |
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.Ala1029=
- Coding
- c.3087G>A
- MANE Select
- NM_207361
- dbSNP
- rs561336798
- Type
- single nucleotide variant
- Location
- chr13:38690431 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
- Residue 1029
- a UniProt-annotated variant site (in cryptop)
Similar variants
- FREM2 p.Ala1029Val Uncertain significance ★★ ⚠ same residue
- 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
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-ala1029 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown