Is FLNC p.Thr2191Pro (c.6571A>C) pathogenic?

FLNC p.Thr2191Pro (c.6571A>C) is classified Uncertain significance in FLNC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-12). AlphaMissense: likely pathogenic (0.7023); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with FLNC p.Thr2191Pro (c.6571A>C)?

FLNC p.Thr2191Pro (c.6571A>C) is associated with Cardiovascular phenotype (ClinVar).

How common is FLNC p.Thr2191Pro (c.6571A>C) in the general population?

FLNC p.Thr2191Pro (c.6571A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLNC p.Thr2191Pro (c.6571A>C)?

AlphaMissense predicts likely pathogenic (score 0.7023) — an in-silico prediction, not a clinical call.

FLNC p.Thr2191Pro

c.6571A>C · rs2536663735 · VCV2565535

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7023 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.7023	likely pathogenic
REVEL	0.587	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 5,636 bp · p 8.4e-23 · regional, not allelic
Overall
CADD	24.8	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

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.Thr2191Pro
Coding: c.6571A>C
MANE Select: NM_001458
dbSNP: rs2536663735
Type: single nucleotide variant
Location: chr7:128854060 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2191: the 'required for interaction with pgm5' region; the 'intradomain insert; mediate targeting to z lines' region

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

Similar variants

FLNC p.Thr2191Met Conflicting classifications of pathogenicity ★ same residue
FLNC p.Thr2191= Likely benign ★★ same residue
FLNC c.1210+1G>A Likely pathogenic ★★ same condition
FLNC c.2550+2T>C Pathogenic/Likely pathogenic ★★ same condition
FLNC c.2930-1G>A Pathogenic/Likely pathogenic ★★ same condition
FLNC c.5199+1G>T Pathogenic/Likely pathogenic ★★ same condition
FLNC c.5398+1G>C Likely pathogenic ★★ same condition
FLNC p.Arg1313Ter 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-thr2191pro (accessed [today's date]).

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