FREM2 p.Ala1703=
c.5109C>T · rs11619157 · VCV702098
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.397%, sas)
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 -3.5 | GERP -4.9 |
| Overall | ||
| CADD | 4.709 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.397%
South Asian · 362/91,078 alleles
Filtering AF
0.364%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.35%
Overall
0.191%
3,076/1,613,698 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.397% | 252 |
| Ashkenazi Jewishnot grpmax-eligible | 0.345% | 290 |
| Middle Eastern | 0.297% | 337 |
| European (non-Finnish) | 0.202% | 496 |
| Remaining individualsnot grpmax-eligible | 0.165% | 607 |
| Finnishnot grpmax-eligible | 0.0737% | 1,357 |
| Admixed American | 0.0716% | 1,396 |
| African / African-American | 0.0267% | 3,751 |
| East Asian | 0.00223% | 44,880 |
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.Ala1703=
- Coding
- c.5109C>T
- MANE Select
- NM_207361
- dbSNP
- rs11619157
- Type
- single nucleotide variant
- Location
- chr13:38692453 (GRCh38)
- Gene constraint
- LOEUF 0.588 · pLI <0.01 (gnomAD)
- Residue 1703
- a UniProt-annotated variant site (in cryptop)
Similar variants
- FREM2 p.Ala1703Thr 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-ala1703 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown