Is FLNC p.Ala1922= (c.5766G>A) pathogenic?

FLNC p.Ala1922= (c.5766G>A) is classified Benign/Likely benign in FLNC (ClinVar, Multiple submitters, 16 submitters; last evaluated 2026-02-03). Rare (popmax 0.445%, mid); Associated with distal myopathy with posterior leg and anterior hand involvement.

How common is FLNC p.Ala1922= (c.5766G>A) in the general population?

FLNC p.Ala1922= (c.5766G>A) is rare (popmax 0.445%, mid) (gnomAD).

FLNC p.Ala1922=

Q: What condition is associated with FLNC p.Ala1922= (c.5766G>A)?

FLNC p.Ala1922= (c.5766G>A) is associated with distal myopathy with posterior leg and anterior hand involvement, cardiomyopathy, myofibrillar myopathy 5 (ClinVar).

Q: How is FLNC-related handgrip and calf weakness-distal myopathy inherited?

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

c.5766G>A · rs58914363 · VCV258150

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

rare (popmax 0.445%, mid)

Conditions

distal myopathy with posterior leg and anterior hand involvement

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 -20
Overall
CADD	0.025	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.445% Middle Eastern · 27/6,062 alleles

Filtering AF 0.314% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.27%

Overall 0.0849% 1,371/1,613,974 alleles · rare exomes 1,216/1,461,646 · genomes 155/152,328 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.445%	225
Admixed American	0.155%	645
Remaining individualsnot grpmax-eligible	0.12%	833
Ashkenazi Jewishnot grpmax-eligible	0.111%	897
African / African-American	0.0973%	1,028
Finnishnot grpmax-eligible	0.0956%	1,046
European (non-Finnish)	0.0836%	1,197
South Asian	0.0198%	5,060
East Asian	0.0111%	8,976

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.Ala1922=
Coding: c.5766G>A
MANE Select: NM_001458
dbSNP: rs58914363
Type: single nucleotide variant
Location: chr7:128851552 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)

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

Disease context

distal myopathy with posterior leg and anterior hand involvement — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy myofibrillar myopathy 5 hypertrophic cardiomyopathy 26

For FLNC-related handgrip and calf weakness-distal myopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult

Similar variants

FLNC p.Ala1922fs Pathogenic ★ same residue
FLNC p.Ala1922Thr Conflicting classifications of pathogenicity ★ 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

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-ala1922 (accessed [today's date]).

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