Is FLNC p.Ser2272= (c.6816C>T) pathogenic?

FLNC p.Ser2272= (c.6816C>T) is classified Benign/Likely benign in FLNC (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-12-08). Ultra-rare (popmax 0.0719%, eas); Associated with myofibrillar myopathy 5.

What condition is associated with FLNC p.Ser2272= (c.6816C>T)?

FLNC p.Ser2272= (c.6816C>T) is associated with myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement, hypertrophic cardiomyopathy 26 (ClinVar).

How common is FLNC p.Ser2272= (c.6816C>T) in the general population?

FLNC p.Ser2272= (c.6816C>T) is ultra-rare (popmax 0.0719%, eas) (gnomAD).

How is Muscle filaminopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

FLNC p.Ser2272=

c.6816C>T · rs375139827 · VCV539518

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0719%, eas)

Conditions

myofibrillar myopathy 5

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 -7.2
Overall
CADD	3.916	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0719% East Asian · 32/44,502 alleles

Filtering AF 0.0523% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0456%

Overall 0.00268% 43/1,604,690 alleles · ultra-rare exomes 38/1,452,410 · genomes 5/152,280 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0719%	1,391
Remaining individualsnot grpmax-eligible	0.00805%	12,428
Admixed American	0.00343%	29,166
African / African-American	0.00134%	74,850
European (non-Finnish)	0.000255%	392,075

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.Ser2272=
Coding: c.6816C>T
MANE Select: NM_001458
dbSNP: rs375139827
Type: single nucleotide variant
Location: chr7:128854501 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2272: the 'required for interaction with pgm5' region

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

Disease context

myofibrillar myopathy 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

For Muscle filaminopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

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
FLNC c.2930-1G>A 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-ser2272 (accessed [today's date]).

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