FREM2 p.Phe2012=
c.6036C>T · rs115455037 · VCV312001
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.69%, 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 | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.96 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.7 | GERP -5.4 |
| Overall | ||
| CADD | 0.423 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.69%
African / African-American · 2,021/74,996 alleles
Filtering AF
2.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.56%
Overall
0.148%
2,395/1,613,550 alleles · low-frequency
exomes 1,145/1,461,346 · genomes 1,250/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.69% | 37 |
| Admixed American | 0.262% | 382 |
| Remaining individualsnot grpmax-eligible | 0.168% | 595 |
| Middle Eastern | 0.0502% | 1,994 |
| South Asian | 0.0132% | 7,589 |
| Finnishnot grpmax-eligible | 0.0109% | 9,139 |
| European (non-Finnish) | 0.00754% | 13,255 |
| East Asian | 0.00223% | 44,840 |
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.Phe2012=
- Coding
- c.6036C>T
- MANE Select
- NM_207361
- dbSNP
- rs115455037
- Type
- single nucleotide variant
- Location
- chr13:38846589 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
- Residue 2012
- the calx-beta 3 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-phe2012 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown