Is FLNC p.Ser792Ile (c.2375G>T) pathogenic?

FLNC p.Ser792Ile (c.2375G>T) is classified Uncertain significance in FLNC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-21). AlphaMissense: ambiguous (0.3571); Ultra-rare (popmax 0.0173%, mid); Associated with Cardiovascular phenotype.

What condition is associated with FLNC p.Ser792Ile (c.2375G>T)?

FLNC p.Ser792Ile (c.2375G>T) is associated with Cardiovascular phenotype, myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

How common is FLNC p.Ser792Ile (c.2375G>T) in the general population?

FLNC p.Ser792Ile (c.2375G>T) is ultra-rare (popmax 0.0173%, mid) (gnomAD).

What do computational predictors say about FLNC p.Ser792Ile (c.2375G>T)?

AlphaMissense predicts ambiguous (score 0.3571) — an in-silico prediction, not a clinical call.

FLNC p.Ser792Ile

c.2375G>T · rs1227658348 · VCV853324

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3571 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, mid)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.3571	ambiguous
REVEL	0.603	indeterminate
SaProt	LLR -11.66	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 11 kb · p 8.4e-13 · regional, not allelic
Overall
CADD	25.0	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 0.0173% Middle Eastern · 1/5,786 alleles

Filtering AF 0.000784% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000622%

Overall 0.00135% 21/1,554,792 alleles · ultra-rare exomes 20/1,402,648 · genomes 1/152,144 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0173%	5,786
Admixed American	0.0039%	25,617
Remaining individualsnot grpmax-eligible	0.00332%	30,108
African / African-American	0.00136%	73,576
European (non-Finnish)	0.00131%	76,591

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.Ser792Ile
Coding: c.2375G>T
MANE Select: NM_001458
dbSNP: rs1227658348
Type: single nucleotide variant
Location: chr7:128842684 (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.Ser792= Conflicting classifications of pathogenicity ★ same residue
FLNC p.Ser792Asn Uncertain significance ★ same residue
FLNC p.Ser792fs Pathogenic ★ 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

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-ser792ile (accessed [today's date]).

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