Is FLNC p.Asp2040= (c.6120C>T) pathogenic?

FLNC p.Asp2040= (c.6120C>T) is classified Benign/Likely benign in FLNC (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-03). Low-frequency (popmax 1.53%, eas); Associated with distal myopathy with posterior leg and anterior hand involvement.

What condition is associated with FLNC p.Asp2040= (c.6120C>T)?

FLNC p.Asp2040= (c.6120C>T) is associated with distal myopathy with posterior leg and anterior hand involvement, myofibrillar myopathy 5, hypertrophic cardiomyopathy 26 (ClinVar).

How common is FLNC p.Asp2040= (c.6120C>T) in the general population?

FLNC p.Asp2040= (c.6120C>T) is low-frequency (popmax 1.53%, eas) (gnomAD).

FLNC p.Asp2040=

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.6120C>T · rs116974302 · VCV383328

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.53%, eas)

Conditions

distal myopathy with posterior leg and anterior hand involvement

⚠ 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 -16
Overall
CADD	3.519	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.53% East Asian · 688/44,876 alleles

Filtering AF 1.44% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4%

Overall 0.0544% 877/1,613,570 alleles · low-frequency exomes 782/1,461,300 · genomes 95/152,270 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.53%	65
South Asian	0.13%	772
Remaining individualsnot grpmax-eligible	0.0848%	1,179
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.00144%	69,413

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.Asp2040=
Coding: c.6120C>T
MANE Select: NM_001458
dbSNP: rs116974302
Type: single nucleotide variant
Location: chr7:128852943 (GRCh38)

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

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-asp2040 (accessed [today's date]).

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