FLNA p.Val709Phe
c.2125G>T · VCV3905520
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
AlphaMissense
ambiguous
0.5197 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/2 damaging
REVEL, SaProt · AlphaMissense indeterminate
Computational evidence
| Protein change | ||
| AlphaMissense | 0.5197 | ambiguous |
|---|---|---|
| REVEL | 0.669 | pathogenic-leaning |
| SaProt | LLR -10.96 | damaging |
| ⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -6.5 | GERP 0.35 |
| Regional constraint | o/e 0.80 | unconstrained · MANE · 6,571 bp · p 2.7e-08 · regional, not allelic |
| Overall | ||
| CADD | 21.5 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- FLNA
- Protein
- p.Val709Phe
- Coding
- c.2125G>T
- MANE Select
- NM_001110556
- Type
- single nucleotide variant
- Location
- chrX:154364270 (GRCh38)
- Structure
- AlphaFold pLDDT 77.37 · 26 PDB
- Residue 709
- a β-strand
Similar variants
- FLNA c.1066-1G>A Pathogenic/Likely pathogenic ★★ same type
- FLNA c.2022+1G>A Pathogenic ★★ same type
- FLNA c.4598+1G>A Pathogenic/Likely pathogenic ★★ same type
- FLNA c.4599-1G>A Pathogenic/Likely pathogenic ★★ same type
- FLNA c.5417-2A>G Likely pathogenic ★★ same type
- FLNA c.5861-2A>G Pathogenic/Likely pathogenic ★★ same type
- FLNA c.868+1G>A Likely pathogenic ★★ same type
- FLNA c.987+1G>A Likely pathogenic ★★ 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/flna-p-val709phe (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown