Is FLNC p.His1263= (c.3789C>T) pathogenic?

FLNC p.His1263= (c.3789C>T) is classified Likely benign in FLNC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-14). Ultra-rare (popmax 0.0165%, mid); Associated with myofibrillar myopathy 5.

What condition is associated with FLNC p.His1263= (c.3789C>T)?

FLNC p.His1263= (c.3789C>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.His1263= (c.3789C>T) in the general population?

FLNC p.His1263= (c.3789C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

How is Muscle filaminopathy inherited?

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

FLNC p.His1263=

c.3789C>T · rs780906350 · VCV392160

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

myofibrillar myopathy 5

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	0.015	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,076 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00112% 18/1,611,284 alleles · ultra-rare exomes 15/1,459,138 · genomes 3/152,146 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,076
Admixed American	0.00834%	11,990
African / African-American	0.00401%	24,957
East Asian	0.00223%	44,866
South Asian	0.0022%	45,479
European (non-Finnish)	0.000509%	196,403

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.His1263=
Coding: c.3789C>T
MANE Select: NM_001458
dbSNP: rs780906350
Type: single nucleotide variant
Location: chr7:128845254 (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

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 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-his1263 (accessed [today's date]).

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