FLRT1 p.Val22Ile
c.64G>A · rs143337663 · VCV530943
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.319%, afr)
Conditions
1
peripheral neuropathy
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.036 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.4 | GERP -0.7, phastCons 1 |
| Regional constraint | o/e 0.78 | unconstrained · MANE · 2,021 bp · p 5.7e-12 · regional, not allelic |
| Overall | ||
| CADD | 16.54 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.319%
African / African-American · 239/74,980 alleles
Filtering AF
0.286%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.273%
Overall
0.0395%
637/1,610,868 alleles · rare
exomes 500/1,458,580 · genomes 137/152,288 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.319% | 314 |
| Remaining individualsnot grpmax-eligible | 0.0593% | 1,687 |
| Middle Eastern | 0.033% | 3,030 |
| European (non-Finnish) | 0.0288% | 3,478 |
| Admixed American | 0.0251% | 3,984 |
| South Asian | 0.00331% | 30,240 |
| Finnishnot grpmax-eligible | 0.0032% | 31,292 |
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.Val22Ile
- Coding
- c.64G>A
- MANE Select
- NM_013280
- dbSNP
- rs143337663
- Type
- single nucleotide variant
- Location
- chr11:64116331 (GRCh38)
- Gene constraint
- LOEUF 0.682 · pLI 0.14 (gnomAD)
- Structure
- AlphaFold pLDDT 73.46
Similar variants
- FLRT1 p.Ala148Gly Uncertain significance ★★ same condition
- FLRT1 p.Ala461Thr Uncertain significance ★★ same condition
- FLRT1 p.Arg149Cys Uncertain significance ★★ same condition
- FLRT1 p.Arg326Lys Uncertain significance ★★ same condition
- FLRT1 p.Arg452His Uncertain significance ★★ same condition
- FLRT1 p.Arg586Gln Uncertain significance ★★ same condition
- FLRT1 p.Arg592Gln Uncertain significance ★★ same condition
- FLRT1 p.Arg592Trp 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/flrt1-p-val22ile (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown