FLRT1 p.Gly558Ser
c.1672G>A · rs150943813 · VCV2401831
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0735%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.294 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.2 | GERP 2, phastCons 1 |
| Regional constraint | o/e 0.78 | unconstrained · MANE · 2,021 bp · p 5.7e-12 · regional, not allelic |
| Overall | ||
| CADD | 23.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0735%
East Asian · 33/44,898 alleles
Filtering AF
0.0537%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.047%
Overall
0.00502%
81/1,613,526 alleles · ultra-rare
exomes 71/1,461,278 · genomes 10/152,248 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0735% | 1,361 |
| Finnishnot grpmax-eligible | 0.00629% | 15,897 |
| Admixed American | 0.005% | 20,003 |
| African / African-American | 0.004% | 24,986 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,237 |
| European (non-Finnish) | 0.00297% | 33,712 |
| South Asian | 0.0011% | 91,084 |
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.Gly558Ser
- Coding
- c.1672G>A
- MANE Select
- NM_013280
- dbSNP
- rs150943813
- Type
- single nucleotide variant
- Location
- chr11:64117939 (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-gly558ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown