Is FLNC p.Ser506= (c.1518C>T) pathogenic?

FLNC p.Ser506= (c.1518C>T) is classified Benign/Likely benign in FLNC (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Rare (popmax 0.445%, sas); Associated with Cardiovascular phenotype.

What condition is associated with FLNC p.Ser506= (c.1518C>T)?

FLNC p.Ser506= (c.1518C>T) is associated with Cardiovascular phenotype, myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

How common is FLNC p.Ser506= (c.1518C>T) in the general population?

FLNC p.Ser506= (c.1518C>T) is rare (popmax 0.445%, sas) (gnomAD).

FLNC p.Ser506=

c.1518C>T · rs368101036 · VCV471979

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.445%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP -9.9
Overall
CADD	4.708	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.445% South Asian · 405/91,088 alleles

Filtering AF 0.409% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.395%

Overall 0.0311% 502/1,614,004 alleles · rare exomes 469/1,461,710 · genomes 33/152,294 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.445%	225
Remaining individualsnot grpmax-eligible	0.032%	3,126
Middle Eastern	0.0165%	6,062
Admixed American	0.01%	10,004
European (non-Finnish)	0.00576%	17,353
East Asian	0.00223%	44,884
African / African-American	0.00133%	75,032

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.Ser506=
Coding: c.1518C>T
MANE Select: NM_001458
dbSNP: rs368101036
Type: single nucleotide variant
Location: chr7:128840129 (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 p.Ser506Asn 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-ser506 (accessed [today's date]).

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