FLRT1 p.Pro475Ala
c.1423C>G · VCV3516048
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00212%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.088 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2, phastCons 1 |
| Regional constraint | o/e 0.78 | unconstrained · MANE · 2,021 bp · p 5.7e-12 · regional, not allelic |
| Overall | ||
| CADD | 18.46 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00212%
European (non-Finnish) · 25/1,179,958 alleles
Filtering AF
0.00145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00123%
Overall
0.00161%
26/1,613,504 alleles · very rare
exomes 24/1,461,246 · genomes 2/152,258 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00212% | 47,198 |
| African / African-American | 0.00133% | 74,958 |
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
- FLRT1
- Protein
- p.Pro475Ala
- Coding
- c.1423C>G
- MANE Select
- NM_013280
- Type
- single nucleotide variant
- Location
- chr11:64117690 (GRCh38)
- Gene constraint
- LOEUF 0.682 · pLI 0.14 (gnomAD)
- Structure
- AlphaFold pLDDT 73.46
- Residue 475
- the fibronectin type-iii domain
Similar variants
- FLRT1 p.Ala148Gly Uncertain significance ★★ same type
- FLRT1 p.Ala461Thr Uncertain significance ★★ same type
- FLRT1 p.Arg149Cys Uncertain significance ★★ same type
- FLRT1 p.Arg326Lys Uncertain significance ★★ same type
- FLRT1 p.Arg452His Uncertain significance ★★ same type
- FLRT1 p.Arg465Gln Uncertain significance ★★ same type
- FLRT1 p.Arg586Gln Uncertain significance ★★ same type
- FLRT1 p.Arg592Gln Uncertain significance ★★ same type
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/flrt1-p-pro475ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown