Is FLNC p.Ser1848= (c.5544C>T) pathogenic?

FLNC p.Ser1848= (c.5544C>T) is classified Conflicting classifications of pathogenicity in FLNC (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-02). Very rare (popmax 0.004%, afr); Associated with myofibrillar myopathy 5.

What condition is associated with FLNC p.Ser1848= (c.5544C>T)?

FLNC p.Ser1848= (c.5544C>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.Ser1848= (c.5544C>T) in the general population?

FLNC p.Ser1848= (c.5544C>T) is very rare (popmax 0.004%, afr) (gnomAD).

How is Muscle filaminopathy inherited?

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

FLNC p.Ser1848=

c.5544C>T · rs1350503435 · VCV759774

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

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 -2.4
Overall
CADD	5.075	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,912 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00031% 5/1,613,940 alleles · very rare exomes 3/1,461,750 · genomes 2/152,190 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,971
Admixed American	0.00167%	60,010
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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.Ser1848=
Coding: c.5544C>T
MANE Select: NM_001458
dbSNP: rs1350503435
Type: single nucleotide variant
Location: chr7:128851236 (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-ser1848 (accessed [today's date]).

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