Is FLNC p.Pro1771Ala (c.5311C>G) pathogenic?

FLNC p.Pro1771Ala (c.5311C>G) is classified Conflicting classifications of pathogenicity in FLNC (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-31). AlphaMissense: likely benign (0.0756); Ultra-rare (popmax 0.0666%, nfe); Associated with myofibrillar myopathy 5.

What condition is associated with FLNC p.Pro1771Ala (c.5311C>G)?

FLNC p.Pro1771Ala (c.5311C>G) is associated with myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement, hypertrophic cardiomyopathy 26 (ClinVar).

How common is FLNC p.Pro1771Ala (c.5311C>G) in the general population?

FLNC p.Pro1771Ala (c.5311C>G) is ultra-rare (popmax 0.0666%, 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.Pro1771Ala (c.5311C>G)?

AlphaMissense predicts likely benign (score 0.0756) — an in-silico prediction, not a clinical call.

FLNC p.Pro1771Ala

c.5311C>G · rs200001272 · VCV389705

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0756 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0666%, nfe)

Conditions

myofibrillar myopathy 5

Computational evidence

Protein change
AlphaMissense	0.0756	likely benign
REVEL	0.339	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 2,000 bp · p 0.0021 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0666% European (non-Finnish) · 786/1,179,554 alleles

Filtering AF 0.0627% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0612%

Overall 0.0511% 824/1,613,586 alleles · ultra-rare exomes 783/1,461,222 · genomes 41/152,364 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0666%	1,501
Remaining individualsnot grpmax-eligible	0.0256%	3,905
Finnishnot grpmax-eligible	0.0203%	4,920
African / African-American	0.00799%	12,510
Admixed American	0.005%	20,010

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.Pro1771Ala
Coding: c.5311C>G
MANE Select: NM_001458
dbSNP: rs200001272
Type: single nucleotide variant
Location: chr7:128850396 (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 p.Pro1771Thr 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-pro1771ala (accessed [today's date]).

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