Is FLNC p.Arg1982Cys (c.5944C>T) pathogenic?

FLNC p.Arg1982Cys (c.5944C>T) is classified Conflicting classifications of pathogenicity in FLNC (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-12-22). AlphaMissense: likely benign (0.1632); Ultra-rare (popmax 0.09%, sas); Associated with myofibrillar myopathy 5.

What condition is associated with FLNC p.Arg1982Cys (c.5944C>T)?

FLNC p.Arg1982Cys (c.5944C>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.Arg1982Cys (c.5944C>T) in the general population?

FLNC p.Arg1982Cys (c.5944C>T) is ultra-rare (popmax 0.09%, sas) (gnomAD).

How is Muscle filaminopathy inherited?

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

What do computational predictors say about FLNC p.Arg1982Cys (c.5944C>T)?

AlphaMissense predicts likely benign (score 0.1632) — an in-silico prediction, not a clinical call.

FLNC p.Arg1982Cys

c.5944C>T · rs538779271 · VCV707276

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1632 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.09%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

myofibrillar myopathy 5

Computational evidence

Protein change
AlphaMissense	0.1632	likely benign
REVEL	0.194	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 5,636 bp · p 8.4e-23 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.09% South Asian · 82/91,088 alleles

Filtering AF 0.0743% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0685%

Overall 0.0115% 185/1,613,310 alleles · ultra-rare exomes 170/1,461,006 · genomes 15/152,304 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.09%	1,111
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.00805%	12,421
Remaining individualsnot grpmax-eligible	0.008%	12,500
East Asian	0.00223%	44,876
African / African-American	0.00133%	75,052

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.Arg1982Cys
Coding: c.5944C>T
MANE Select: NM_001458
dbSNP: rs538779271
Type: single nucleotide variant
Location: chr7:128852692 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1982: 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 p.Arg1982His 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-arg1982cys (accessed [today's date]).

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