Is FLNC p.Pro1990Ser (c.5968C>T) pathogenic?

FLNC p.Pro1990Ser (c.5968C>T) is classified Uncertain significance in FLNC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-02). AlphaMissense: likely benign (0.3074); Ultra-rare (popmax 0.0557%, eas); Associated with hypertrophic cardiomyopathy 26.

What condition is associated with FLNC p.Pro1990Ser (c.5968C>T)?

FLNC p.Pro1990Ser (c.5968C>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.Pro1990Ser (c.5968C>T) in the general population?

FLNC p.Pro1990Ser (c.5968C>T) is ultra-rare (popmax 0.0557%, eas) (gnomAD).

What do computational predictors say about FLNC p.Pro1990Ser (c.5968C>T)?

AlphaMissense predicts likely benign (score 0.3074) — an in-silico prediction, not a clinical call.

FLNC p.Pro1990Ser

c.5968C>T · VCV3761146

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3074 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0557%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

hypertrophic cardiomyopathy 26

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.3074	likely benign
REVEL	0.285	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.66	unconstrained · MANE · 5,636 bp · p 8.4e-23 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0557% East Asian · 25/44,864 alleles

Filtering AF 0.0387% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.033%

Overall 0.00192% 31/1,613,234 alleles · ultra-rare exomes 31/1,460,940 · genomes 0/152,294 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0557%	1,795
European (non-Finnish)	0.000509%	196,638

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.Pro1990Ser
Coding: c.5968C>T
MANE Select: NM_001458
Type: single nucleotide variant
Location: chr7:128852716 (GRCh38)

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

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-pro1990ser (accessed [today's date]).

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