Is FLNC p.Arg2018Ser (c.6052C>A) pathogenic?

FLNC p.Arg2018Ser (c.6052C>A) is classified Uncertain significance in FLNC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-03-01). AlphaMissense: likely pathogenic (0.5754); Absent from gnomAD v4.1; Associated with FLNC-related disorder.

What condition is associated with FLNC p.Arg2018Ser (c.6052C>A)?

FLNC p.Arg2018Ser (c.6052C>A) is associated with FLNC-related disorder (ClinVar).

How common is FLNC p.Arg2018Ser (c.6052C>A) in the general population?

FLNC p.Arg2018Ser (c.6052C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLNC p.Arg2018Ser (c.6052C>A)?

AlphaMissense predicts likely pathogenic (score 0.5754) — an in-silico prediction, not a clinical call.

FLNC p.Arg2018Ser

c.6052C>A · rs1335627502 · VCV3061057

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5754 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

FLNC-related disorder

Computational evidence

Protein change
AlphaMissense	0.5754	likely pathogenic
REVEL	0.117	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	phastCons 0.93
Regional constraint	o/e 0.66	unconstrained · MANE · 5,636 bp · p 8.4e-23 · regional, not allelic
Overall
CADD	24.7	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.Arg2018Ser
Coding: c.6052C>A
MANE Select: NM_001458
dbSNP: rs1335627502
Type: single nucleotide variant
Location: chr7:128852875 (GRCh38)
Gene constraint: LOEUF 0.424 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2018: the 'required for interaction with pgm5' region

Full FLNC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

FLNC-related disorder

Similar variants

FLNC p.Arg2018His Conflicting classifications of pathogenicity ★ ⚠ same residue
FLNC c.4457-1G>C Pathogenic ★★ same condition
FLNC c.7385-1G>A Likely pathogenic ★★ same condition
FLNC c.7780+1G>C Likely pathogenic ★★ same condition
FLNC p.Ala1186Val Pathogenic/Likely pathogenic ★★ same condition
FLNC p.Gln1315Ter Pathogenic/Likely pathogenic ★★ same condition
FLNC p.Ala1105Ser Uncertain significance ★★ same condition
FLNC p.Ala2485Val Uncertain significance ★★ 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-arg2018ser (accessed [today's date]).

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