Is FLNC p.Ser2405= (c.7215G>A) pathogenic?

FLNC p.Ser2405= (c.7215G>A) is classified Benign/Likely benign in FLNC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-06-01). Ultra-rare (popmax 0.0267%, eas); Associated with myofibrillar myopathy 5.

What condition is associated with FLNC p.Ser2405= (c.7215G>A)?

FLNC p.Ser2405= (c.7215G>A) is associated with myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement, hypertrophic cardiomyopathy 26 (ClinVar).

How common is FLNC p.Ser2405= (c.7215G>A) in the general population?

FLNC p.Ser2405= (c.7215G>A) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

How is Muscle filaminopathy inherited?

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

FLNC p.Ser2405=

c.7215G>A · rs774019775 · VCV472163

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Conditions

myofibrillar myopathy 5

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -12
Overall
CADD	0.24	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% East Asian · 12/44,892 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.00155% 25/1,613,598 alleles · ultra-rare exomes 21/1,461,444 · genomes 4/152,154 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,741
Admixed American	0.00833%	12,002
Remaining individualsnot grpmax-eligible	0.0016%	62,472
South Asian	0.0011%	91,060
European (non-Finnish)	0.000509%	196,635

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.Ser2405=
Coding: c.7215G>A
MANE Select: NM_001458
dbSNP: rs774019775
Type: single nucleotide variant
Location: chr7:128855278 (GRCh38)

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

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-ser2405 (accessed [today's date]).

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