FREM2 p.Val73=
c.219G>A · rs115510540 · VCV1628444
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0269%, eas)
Conditions
2
isolated cryptophthalmia
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 1.7 | GERP -0.54, phastCons 0.96 |
| Overall | ||
| CADD | 9.287 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0269%
East Asian · 12/44,648 alleles
Filtering AF
0.0155%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0121%
Overall
0.00218%
35/1,603,042 alleles · ultra-rare
exomes 29/1,450,726 · genomes 6/152,316 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0269% | 3,721 |
| South Asian | 0.00672% | 14,891 |
| Remaining individualsnot grpmax-eligible | 0.00646% | 15,482 |
| European (non-Finnish) | 0.00111% | 90,338 |
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.Val73=
- Coding
- c.219G>A
- MANE Select
- NM_207361
- dbSNP
- rs115510540
- Type
- single nucleotide variant
- Location
- chr13:38687563 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
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-val73 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown