Is FLNC p.Pro486= (c.1458C>A) pathogenic?

FLNC p.Pro486= (c.1458C>A) is classified Benign in FLNC (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). Common (popmax 30.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with FLNC p.Pro486= (c.1458C>A)?

FLNC p.Pro486= (c.1458C>A) is associated with Cardiovascular phenotype, myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

FLNC p.Pro486=

Q: How common is FLNC p.Pro486= (c.1458C>A) in the general population?

FLNC p.Pro486= (c.1458C>A) is common (popmax 30.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1458C>A · rs2291563 · VCV129080

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Common

common (popmax 30.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Cardiovascular phenotype

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 1.4	phastCons 1
Overall
CADD	11.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.9% African / African-American · 23,143/75,012 alleles

Filtering AF 30.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 30.4%

Overall 4.54% 73,350/1,614,004 alleles · common exomes 55,618/1,461,710 · genomes 17,732/152,294 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	30.9%	3
East Asian	28.3%	4
Admixed American	11.3%	9
South Asian	7.06%	14
Remaining individualsnot grpmax-eligible	5.74%	17
Middle Eastern	3.08%	32
Ashkenazi Jewishnot grpmax-eligible	2.53%	39
Finnishnot grpmax-eligible	2.46%	41
European (non-Finnish)	1.54%	65
Amishnot grpmax-eligible	0.219%	456

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.Pro486=
Coding: c.1458C>A
MANE Select: NM_001458
dbSNP: rs2291563
Type: single nucleotide variant
Location: chr7:128840069 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: myofibrillar myopathy 5 distal myopathy with posterior leg and anterior hand involvement hypertrophic cardiomyopathy 26

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-pro486 (accessed [today's date]).

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