FLRT1 p.Val349Met
c.1045G>A · rs779105954 · VCV3095686
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.024%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.087 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.1 | GERP -2.9, phastCons 1 |
| Regional constraint | o/e 0.78 | unconstrained · MANE · 2,021 bp · p 5.7e-12 · regional, not allelic |
| Overall | ||
| CADD | 23.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.024%
African / African-American · 18/74,958 alleles
Filtering AF
0.0155%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0128%
Overall
0.00186%
30/1,614,018 alleles · ultra-rare
exomes 21/1,461,748 · genomes 9/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.024% | 4,164 |
| South Asian | 0.00439% | 22,772 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,239 |
| East Asian | 0.00223% | 44,888 |
| European (non-Finnish) | 0.000424% | 236,005 |
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.Val349Met
- Coding
- c.1045G>A
- MANE Select
- NM_013280
- dbSNP
- rs779105954
- Type
- single nucleotide variant
- Location
- chr11:64117312 (GRCh38)
- Gene constraint
- LOEUF 0.682 · pLI 0.14 (gnomAD)
- Structure
- AlphaFold pLDDT 73.46
- Residue 349
- the lrrct 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-val349met (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown