Is FLNC p.Arg1313Pro (c.3938G>C) pathogenic?

FLNC p.Arg1313Pro (c.3938G>C) is classified Uncertain significance in FLNC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-08). AlphaMissense: likely pathogenic (0.8607); Absent from gnomAD v4.1; Associated with hypertrophic cardiomyopathy 26.

What condition is associated with FLNC p.Arg1313Pro (c.3938G>C)?

FLNC p.Arg1313Pro (c.3938G>C) is associated with hypertrophic cardiomyopathy 26, myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

How common is FLNC p.Arg1313Pro (c.3938G>C) in the general population?

FLNC p.Arg1313Pro (c.3938G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLNC p.Arg1313Pro (c.3938G>C)?

AlphaMissense predicts likely pathogenic (score 0.8607) — an in-silico prediction, not a clinical call.

FLNC p.Arg1313Pro

c.3938G>C · rs199804244 · VCV1506515

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8607 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypertrophic cardiomyopathy 26

Computational evidence

Protein change
AlphaMissense	0.8607	likely pathogenic
REVEL	0.659	pathogenic-leaning
SaProt	LLR -11.21	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.6	phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 11 kb · p 8.4e-13 · regional, not allelic
Overall
CADD	25.5	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FLNC
Protein: p.Arg1313Pro
Coding: c.3938G>C
MANE Select: NM_001458
dbSNP: rs199804244
Type: single nucleotide variant
Location: chr7:128846137 (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.Arg1313Ter Pathogenic/Likely pathogenic ★★ same residue
FLNC p.Arg1313Gln Conflicting classifications of pathogenicity ★ same residue
FLNC p.Arg1313Gly Uncertain significance ★ ⚠ same residue
FLNC p.Arg1313Leu Uncertain significance ★ same residue
FLNC p.Arg1313= Likely benign ★ same residue
FLNC p.Arg1313fs Pathogenic/Likely pathogenic ★★ same residue
FLNC c.1047+1G>T Likely pathogenic ★★ same condition
FLNC c.1048-1G>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-arg1313pro (accessed [today's date]).

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