Is FLNC p.Pro1102Ser (c.3304C>T) pathogenic?

FLNC p.Pro1102Ser (c.3304C>T) is classified Conflicting classifications of pathogenicity in FLNC (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-04-14). AlphaMissense: likely pathogenic (0.8458); Ultra-rare (popmax 0.0309%, nfe); Associated with myofibrillar myopathy 5.

What condition is associated with FLNC p.Pro1102Ser (c.3304C>T)?

FLNC p.Pro1102Ser (c.3304C>T) is associated with myofibrillar myopathy 5, cardiomyopathy, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

How common is FLNC p.Pro1102Ser (c.3304C>T) in the general population?

FLNC p.Pro1102Ser (c.3304C>T) is ultra-rare (popmax 0.0309%, nfe) (gnomAD).

How is Muscle filaminopathy inherited?

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

What do computational predictors say about FLNC p.Pro1102Ser (c.3304C>T)?

AlphaMissense predicts likely pathogenic (score 0.8458) — an in-silico prediction, not a clinical call.

FLNC p.Pro1102Ser

c.3304C>T · rs199707920 · VCV539421

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.8458 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0309%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

myofibrillar myopathy 5

Computational evidence

Protein change
AlphaMissense	0.8458	likely pathogenic
REVEL	0.934	strongly pathogenic-leaning
SaProt	LLR -13.37	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 11 kb · p 8.4e-13 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0309% European (non-Finnish) · 365/1,180,036 alleles

Filtering AF 0.0283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0273%

Overall 0.0239% 385/1,613,934 alleles · ultra-rare exomes 361/1,461,712 · genomes 24/152,222 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0309%	3,233
Remaining individualsnot grpmax-eligible	0.0192%	5,206
Admixed American	0.00833%	12,002
African / African-American	0.00267%	37,468
South Asian	0.0011%	91,092

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.Pro1102Ser
Coding: c.3304C>T
MANE Select: NM_001458
dbSNP: rs199707920
Type: single nucleotide variant
Location: chr7:128844769 (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: cardiomyopathy distal myopathy with posterior leg and anterior hand involvement hypertrophic cardiomyopathy 26

For Muscle filaminopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

FLNC p.Pro1102Leu Uncertain significance ★★ ⚠ 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-pro1102ser (accessed [today's date]).

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