Is FLNC p.Ser2016= (c.6048C>T) pathogenic?

FLNC p.Ser2016= (c.6048C>T) is classified Conflicting classifications of pathogenicity in FLNC (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-06-28). Ultra-rare (popmax 0.0223%, eas); Associated with hypertrophic cardiomyopathy 26.

What condition is associated with FLNC p.Ser2016= (c.6048C>T)?

FLNC p.Ser2016= (c.6048C>T) is associated with hypertrophic cardiomyopathy 26, cardiomyopathy, myofibrillar myopathy 5 (ClinVar).

How common is FLNC p.Ser2016= (c.6048C>T) in the general population?

FLNC p.Ser2016= (c.6048C>T) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

FLNC p.Ser2016=

c.6048C>T · rs369991887 · VCV1118725

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Conditions

hypertrophic cardiomyopathy 26

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 -5.3
Overall
CADD	10.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0223% East Asian · 10/44,888 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00916%

Overall 0.00204% 33/1,613,812 alleles · ultra-rare exomes 27/1,461,504 · genomes 6/152,308 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,489
African / African-American	0.008%	12,506
Remaining individualsnot grpmax-eligible	0.0032%	31,252
Admixed American	0.00167%	60,024
European (non-Finnish)	0.00119%	84,289

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.Ser2016=
Coding: c.6048C>T
MANE Select: NM_001458
dbSNP: rs369991887
Type: single nucleotide variant
Location: chr7:128852871 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2016: the 'required for interaction with pgm5' region

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

Disease context

hypertrophic cardiomyopathy 26 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

FLNC p.Ser2016Ile 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
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-ser2016 (accessed [today's date]).

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