Is FLNC p.His49= (c.147C>T) pathogenic?

FLNC p.His49= (c.147C>T) is classified Benign in FLNC (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). Common (popmax 18.4%, eas) — too common for a highly-penetrant pathogenic allele; Associated with myofibrillar myopathy 5.

What condition is associated with FLNC p.His49= (c.147C>T)?

FLNC p.His49= (c.147C>T) is associated with myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement, hypertrophic cardiomyopathy 26 (ClinVar).

How is Muscle filaminopathy inherited?

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

FLNC p.His49=

Q: How common is FLNC p.His49= (c.147C>T) in the general population?

FLNC p.His49= (c.147C>T) is common (popmax 18.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.147C>T · rs3734972 · VCV129081

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Common

common (popmax 18.4%, eas) — too common for a highly-penetrant pathogenic allele

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 0.17	phastCons 0.96
Overall
CADD	7.71	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 18.4% East Asian · 8,265/44,856 alleles

Filtering AF 18.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 18%

Overall 8.9% 143,473/1,612,946 alleles · common exomes 129,166/1,460,644 · genomes 14,307/152,302 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	18.4%	5
African / African-American	9.95%	10
Ashkenazi Jewishnot grpmax-eligible	9.17%	11
Remaining individualsnot grpmax-eligible	9.08%	11
Admixed American	8.94%	11
South Asian	8.81%	11
European (non-Finnish)	8.49%	12
Middle Eastern	8.35%	12
Finnishnot grpmax-eligible	8.31%	12
Amishnot grpmax-eligible	7.35%	14

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.His49=
Coding: c.147C>T
MANE Select: NM_001458
dbSNP: rs3734972
Type: single nucleotide variant
Location: chr7:128830784 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 49: the calponin-homology (ch) 1 domain; the 'actin-binding' region

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-his49 (accessed [today's date]).

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