FLRT1 p.Arg127His
c.380G>A · rs200610220 · VCV3095697
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.02%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.043 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.6 | GERP -4, phastCons 0.55 |
| Regional constraint | o/e 0.78 | unconstrained · MANE · 2,021 bp · p 5.7e-12 · regional, not allelic |
| Overall | ||
| CADD | 21.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.02%
African / African-American · 15/75,048 alleles
Filtering AF
0.0123%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00987%
Overall
0.0018%
29/1,614,014 alleles · ultra-rare
exomes 18/1,461,702 · genomes 11/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.02% | 5,003 |
| Admixed American | 0.00333% | 30,012 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,498 |
| South Asian | 0.0011% | 91,080 |
| European (non-Finnish) | 0.000847% | 117,999 |
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.Arg127His
- Coding
- c.380G>A
- MANE Select
- NM_013280
- dbSNP
- rs200610220
- Type
- single nucleotide variant
- Location
- chr11:64116647 (GRCh38)
- Gene constraint
- LOEUF 0.682 · pLI 0.14 (gnomAD)
- Structure
- AlphaFold pLDDT 73.46
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-arg127his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown