Is FLNC p.Leu165fs (c.488_491dup) pathogenic?

FLNC p.Leu165fs (c.488491dup) is classified Pathogenic in FLNC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-05). No gnomAD frequency available for this variant; Associated with Cardiovascular phenotype.

What condition is associated with FLNC p.Leu165fs (c.488_491dup)?

FLNC p.Leu165fs (c.488_491dup) is associated with Cardiovascular phenotype (ClinVar).

How common is FLNC p.Leu165fs (c.488_491dup) in the general population?

FLNC p.Leu165fs (c.488_491dup) is no gnomAD frequency available for this variant (gnomAD).

FLNC p.Leu165fs

c.488_491dup · rs2536614690 · VCV1743791

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FLNC
Protein: p.Leu165fs
Coding: c.488_491dup
MANE Select: NM_001458
dbSNP: rs2536614690
Type: Duplication
Location: chr7:128835460 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 165: the calponin-homology (ch) 2 domain; the 'actin-binding' 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.Leu165= Likely benign ★ same residue
FLNC p.Glu365Ter Pathogenic ★★ same condition
FLNC p.Thr1684fs Pathogenic ★★ same condition
FLNC p.Tyr1316fs Pathogenic ★★ same condition
FLNC p.Arg437fs Likely pathogenic ★ same condition
FLNC p.Glu508fs Pathogenic ★ same condition
FLNC p.Gly1020fs Likely pathogenic ★ same condition
FLNC p.Gly201fs 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-leu165fs (accessed [today's date]).

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