FREM2 p.Ser2732=
c.8196C>T · rs151062281 · VCV312025
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.106%, nfe)
Conditions
1
Fraser syndrome 2
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>G here scores Δ0.39 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4.7 | GERP 1.8, phastCons 1 |
| Overall | ||
| CADD | 8.047 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.106%
European (non-Finnish) · 1,248/1,179,794 alleles
Filtering AF
0.101%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0989%
Overall
0.0811%
1,309/1,613,924 alleles · rare
exomes 1,257/1,461,596 · genomes 52/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.106% | 945 |
| Finnishnot grpmax-eligible | 0.0406% | 2,463 |
| Remaining individualsnot grpmax-eligible | 0.0384% | 2,604 |
| African / African-American | 0.012% | 8,337 |
| Admixed American | 0.00333% | 30,013 |
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.Ser2732=
- Coding
- c.8196C>T
- MANE Select
- NM_207361
- dbSNP
- rs151062281
- Type
- single nucleotide variant
- Location
- chr13:38874501 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
- Residue 2732
- 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-ser2732 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown