Is FLNC p.Pro1828Ser (c.5482C>T) pathogenic?

FLNC p.Pro1828Ser (c.5482C>T) is classified Uncertain significance in FLNC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-29). AlphaMissense: likely pathogenic (0.9627); Very rare (popmax 0.00167%, amr); Associated with hypertrophic cardiomyopathy 26.

What condition is associated with FLNC p.Pro1828Ser (c.5482C>T)?

FLNC p.Pro1828Ser (c.5482C>T) is associated with hypertrophic cardiomyopathy 26, myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

How common is FLNC p.Pro1828Ser (c.5482C>T) in the general population?

FLNC p.Pro1828Ser (c.5482C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about FLNC p.Pro1828Ser (c.5482C>T)?

AlphaMissense predicts likely pathogenic (score 0.9627) — an in-silico prediction, not a clinical call.

FLNC p.Pro1828Ser

c.5482C>T · VCV3761335

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9627 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

hypertrophic cardiomyopathy 26

Computational evidence

Protein change
AlphaMissense	0.9627	likely pathogenic
REVEL	0.686	pathogenic-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 2,000 bp · p 0.0021 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,958 alleles

Overall 0.000124% 2/1,613,616 alleles · very rare exomes 2/1,461,662 · genomes 0/151,954 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,958
South Asian	0.0011%	91,016

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.Pro1828Ser
Coding: c.5482C>T
MANE Select: NM_001458
Type: single nucleotide variant
Location: chr7:128850886 (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

hypertrophic cardiomyopathy 26 — 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

Similar variants

FLNC p.Pro1828= Likely benign ★ same residue
FLNC p.Pro1828Arg 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

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-pro1828ser (accessed [today's date]).

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