Is FLNC p.His2601= (c.7803C>T) pathogenic?

FLNC p.His2601= (c.7803C>T) is classified Likely benign in FLNC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-17). Ultra-rare (popmax 0.0357%, amr); Associated with Cardiovascular phenotype.

What condition is associated with FLNC p.His2601= (c.7803C>T)?

FLNC p.His2601= (c.7803C>T) is associated with Cardiovascular phenotype, myofibrillar myopathy 5, distal myopathy with posterior leg and anterior hand involvement (ClinVar).

How common is FLNC p.His2601= (c.7803C>T) in the general population?

FLNC p.His2601= (c.7803C>T) is ultra-rare (popmax 0.0357%, amr) (gnomAD).

FLNC p.His2601=

c.7803C>T · rs749737805 · VCV472181

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0357%, amr)

Conditions

Cardiovascular phenotype

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.3	phastCons 1
Overall
CADD	7.416	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0357% Admixed American · 20/56,082 alleles

Filtering AF 0.0236% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00451% 70/1,552,224 alleles · ultra-rare exomes 53/1,400,020 · genomes 17/152,204 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0357%	2,804
European (non-Finnish)	0.00414%	24,156
Finnishnot grpmax-eligible	0.00325%	30,814
Remaining individualsnot grpmax-eligible	0.00166%	60,286

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.His2601=
Coding: c.7803C>T
MANE Select: NM_001458
dbSNP: rs749737805
Type: single nucleotide variant
Location: chr7:128858030 (GRCh38)

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

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-his2601 (accessed [today's date]).

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