FRAS1 p.Pro2015His
c.6044C>A · VCV3591047
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00102%, nfe)
Conditions
1
Fraser syndrome 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.285 | benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 2.7 | GERP 1.5, phastCons 0.17 |
| Regional constraint | o/e 0.97 | unconstrained · MANE · 483 kb · p 0.045 · regional, not allelic |
| Overall | ||
| CADD | 21.9 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00102%
European (non-Finnish) · 12/1,179,326 alleles
Filtering AF
0.000543%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000429%
Overall
0.000744%
12/1,612,618 alleles · very rare
exomes 12/1,460,322 · genomes 0/152,296 · joint denominator
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
- FRAS1
- Protein
- p.Pro2015His
- Coding
- c.6044C>A
- MANE Select
- NM_025074
- Type
- single nucleotide variant
- Location
- chr4:78448086 (GRCh38)
- Gene constraint
- LOEUF 0.729 · pLI <0.01 (gnomAD)
Similar variants
- FRAS1 p.Pro2015Leu Uncertain significance ★ same residue
- FRAS1 c.1072-1G>C Likely pathogenic ★★ same condition
- FRAS1 c.11298+1G>A Pathogenic/Likely pathogenic ★★ same condition
- FRAS1 c.2722+1G>A Pathogenic/Likely pathogenic ★★ same condition
- FRAS1 c.310-1G>A Likely pathogenic ★★ same condition
- FRAS1 c.3152-2A>G Likely pathogenic ★★ same condition
- FRAS1 c.3563+1G>A Pathogenic ★★ same condition
- FRAS1 c.7522+1G>T Pathogenic ★★ 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/fras1-p-pro2015his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown