Is FLNC p.Asp1000= (c.3000T>C) pathogenic?

FLNC p.Asp1000= (c.3000T>C) is classified Benign/Likely benign in FLNC (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-05-01). Rare (popmax 0.28%, mid); Associated with distal myopathy with posterior leg and anterior hand involvement.

What condition is associated with FLNC p.Asp1000= (c.3000T>C)?

FLNC p.Asp1000= (c.3000T>C) is associated with distal myopathy with posterior leg and anterior hand involvement, myofibrillar myopathy 5, hypertrophic cardiomyopathy 26 (ClinVar).

How common is FLNC p.Asp1000= (c.3000T>C) in the general population?

FLNC p.Asp1000= (c.3000T>C) is rare (popmax 0.28%, mid) (gnomAD).

FLNC p.Asp1000=

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.3000T>C · rs184454068 · VCV258139

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Rare

rare (popmax 0.28%, 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -8.9
Overall
CADD	0.687	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.28% Middle Eastern · 17/6,062 alleles

Filtering AF 0.179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.147%

Overall 0.0865% 1,396/1,614,014 alleles · rare exomes 1,234/1,461,688 · genomes 162/152,326 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.28%	357
Ashkenazi Jewishnot grpmax-eligible	0.243%	411
Finnishnot grpmax-eligible	0.163%	614
South Asian	0.0966%	1,035
European (non-Finnish)	0.0885%	1,130
Remaining individualsnot grpmax-eligible	0.0784%	1,276
Admixed American	0.025%	4,002
African / African-American	0.00799%	12,510
East Asian	0.00223%	44,884

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.Asp1000=
Coding: c.3000T>C
MANE Select: NM_001458
dbSNP: rs184454068
Type: single nucleotide variant
Location: chr7:128844074 (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: 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.Asp1000Ala 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
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-asp1000 (accessed [today's date]).

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