Is FLNC p.Pro1525Ser (c.4573C>T) pathogenic?

FLNC p.Pro1525Ser (c.4573C>T) is classified Uncertain significance in FLNC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-22). AlphaMissense: likely benign (0.2455); No allele count reported in gnomAD v4.1 (AN 1,603,442); Associated with Cardiovascular phenotype.

What condition is associated with FLNC p.Pro1525Ser (c.4573C>T)?

FLNC p.Pro1525Ser (c.4573C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is FLNC p.Pro1525Ser (c.4573C>T) in the general population?

FLNC p.Pro1525Ser (c.4573C>T) is no allele count reported in gnomAD v4.1 (AN 1,603,442) (gnomAD).

What do computational predictors say about FLNC p.Pro1525Ser (c.4573C>T)?

AlphaMissense predicts likely benign (score 0.2455) — an in-silico prediction, not a clinical call.

FLNC p.Pro1525Ser

c.4573C>T · rs2536646704 · VCV3221731

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2455 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,603,442)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.2455	likely benign
REVEL	0.875	moderately pathogenic-leaning
SaProt	LLR -11.74	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 11 kb · p 8.4e-13 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,603,442). 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.Pro1525Ser
Coding: c.4573C>T
MANE Select: NM_001458
dbSNP: rs2536646704
Type: single nucleotide variant
Location: chr7:128848061 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLNC p.Pro1525= 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
FLNC p.Arg1341Ter 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-pro1525ser (accessed [today's date]).

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