Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 10 submitters
gnomAD v4.1
Common
common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
3
hypertrophic cardiomyopathy 26
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.7 | phastCons 1 |
| Overall | ||
| CADD | 12.83 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
100%
East Asian · 44,886/44,886 alleles
Filtering AF
99.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 99.8%
Overall
99.8%
1,611,350/1,614,052 alleles · common
exomes 1,460,313/1,461,710 · genomes 151,037/152,342 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 100% | 1 |
| Finnishnot grpmax-eligible | 100% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 100% | 1 |
| Amishnot grpmax-eligible | 100% | 1 |
| South Asian | 100% | 1 |
| European (non-Finnish) | 100% | 1 |
| Admixed American | 99.8% | 1 |
| Remaining individualsnot grpmax-eligible | 99.8% | 1 |
| Middle Eastern | 99.8% | 1 |
| African / African-American | 97% | 1 |
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
- FLNC
- Protein
- p.Asp1468=
- Coding
- c.4404T>C
- MANE Select
- NM_001458
- dbSNP
- rs2249128
- Type
- single nucleotide variant
- Location
- chr7:128847812 (GRCh38)
- Gene constraint
- LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Similar variants
- FLNC p.Asp1468Asn Conflicting classifications of pathogenicity ★ ⚠ same residue
- FLNC c.1047+1G>T Likely pathogenic ★★ same condition
- FLNC c.1048-1G>A Likely pathogenic ★★ same condition
- FLNC c.1210+1G>A Likely pathogenic ★★ same condition
- FLNC c.1549+2T>G Likely pathogenic ★★ same condition
- FLNC c.2007+1G>A Likely pathogenic ★★ same condition
- FLNC c.2550+1G>C Likely pathogenic ★★ same condition
- FLNC c.2550+2T>C Pathogenic/Likely pathogenic ★★ 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/flnc-p-asp1468 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown