Is FLNC p.Asp2407= (c.7221C>T) pathogenic?

FLNC p.Asp2407= (c.7221C>T) is classified Benign in FLNC (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-04). Common (popmax 38%, afr) — too common for a highly-penetrant pathogenic allele; Associated with distal myopathy with posterior leg and anterior hand involvement.

What condition is associated with FLNC p.Asp2407= (c.7221C>T)?

FLNC p.Asp2407= (c.7221C>T) is associated with distal myopathy with posterior leg and anterior hand involvement, myofibrillar myopathy 5, hypertrophic cardiomyopathy 26 (ClinVar).

FLNC p.Asp2407=

Q: How common is FLNC p.Asp2407= (c.7221C>T) in the general population?

FLNC p.Asp2407= (c.7221C>T) is common (popmax 38%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.7221C>T · rs3816885 · VCV129097

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Common

common (popmax 38%, afr) — too common for a highly-penetrant pathogenic allele

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 -16
Overall
CADD	0.169	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 38% African / African-American · 28,475/74,836 alleles

Filtering AF 37.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 37.5%

Overall 7.59% 122,472/1,612,590 alleles · common exomes 98,835/1,460,440 · genomes 23,637/152,150 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	38%	3
East Asian	33.5%	3
South Asian	16.8%	6
Admixed American	14.4%	7
Remaining individualsnot grpmax-eligible	8.62%	12
Middle Eastern	4.95%	20
European (non-Finnish)	3.99%	25
Finnishnot grpmax-eligible	2.65%	38
Ashkenazi Jewishnot grpmax-eligible	1.79%	56
Amishnot grpmax-eligible	0.33%	303

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.Asp2407=
Coding: c.7221C>T
MANE Select: NM_001458
dbSNP: rs3816885
Type: single nucleotide variant
Location: chr7:128855284 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2407: an α-helix; the 'interaction with inppl1' region

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: 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 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-asp2407 (accessed [today's date]).

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