Is FLNC p.Ser1806= (c.5418G>A) pathogenic?

FLNC p.Ser1806= (c.5418G>A) is classified Conflicting classifications of pathogenicity in FLNC (ClinVar, Conflicting submitters, 12 submitters; last evaluated 2026-01-27). Rare (popmax 0.275%, afr); Associated with Cardiovascular phenotype.

What condition is associated with FLNC p.Ser1806= (c.5418G>A)?

FLNC p.Ser1806= (c.5418G>A) is associated with Cardiovascular phenotype, myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

How common is FLNC p.Ser1806= (c.5418G>A) in the general population?

FLNC p.Ser1806= (c.5418G>A) is rare (popmax 0.275%, afr) (gnomAD).

FLNC p.Ser1806=

c.5418G>A · rs376078394 · VCV290873

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

rare (popmax 0.275%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11
Overall
CADD	1.187	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.275% African / African-American · 206/74,998 alleles

Filtering AF 0.244% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.232%

Overall 0.0185% 298/1,613,744 alleles · rare exomes 164/1,461,546 · genomes 134/152,198 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.275%	364
Remaining individualsnot grpmax-eligible	0.0336%	2,976
Middle Eastern	0.033%	3,031
South Asian	0.022%	4,553
Admixed American	0.00667%	15,001
European (non-Finnish)	0.00381%	26,222

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.Ser1806=
Coding: c.5418G>A
MANE Select: NM_001458
dbSNP: rs376078394
Type: single nucleotide variant
Location: chr7:128850822 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

Full FLNC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: myofibrillar myopathy 5 distal myopathy with posterior leg and anterior hand involvement hypertrophic cardiomyopathy 26

Similar variants

FLNC p.Ser1806Ter Pathogenic/Likely pathogenic ★★ same residue
FLNC p.Ser1806Leu Uncertain significance ★★ ⚠ same residue
FLNC p.Ser1806Pro Uncertain significance ★ ⚠ 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

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-ser1806 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown