Is FLNA p.Arg2003Cys (c.6007C>T) pathogenic?

FLNA p.Arg2003Cys (c.6007C>T) is classified Uncertain significance in FLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-20). AlphaMissense: likely benign (0.2931); Very rare (popmax 0.00435%, amr); Associated with FLNA-related disorder.

What condition is associated with FLNA p.Arg2003Cys (c.6007C>T)?

FLNA p.Arg2003Cys (c.6007C>T) is associated with FLNA-related disorder (ClinVar).

How common is FLNA p.Arg2003Cys (c.6007C>T) in the general population?

FLNA p.Arg2003Cys (c.6007C>T) is very rare (popmax 0.00435%, amr) (gnomAD).

What do computational predictors say about FLNA p.Arg2003Cys (c.6007C>T)?

AlphaMissense predicts likely benign (score 0.2931) — an in-silico prediction, not a clinical call.

FLNA p.Arg2003Cys

c.6007C>T · rs2067636406 · VCV2637317

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2931 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00435%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

FLNA-related disorder

Computational evidence

Protein change
AlphaMissense	0.2931	likely benign
REVEL	0.299	indeterminate
SaProt	LLR -9.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.58 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 11 kb · p 3.1e-20 · regional, not allelic
Overall
CADD	25.2	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00435% Admixed American · 2/46,001 alleles

Filtering AF 0.000721% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00027%

Overall 0.000661% 8/1,210,676 alleles · very rare exomes 6/1,097,748 · genomes 2/112,928 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00435%	23,001
East Asian	0.00296%	33,800
African / African-American	0.00174%	57,506
European (non-Finnish)	0.000447%	223,847

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: FLNA
Protein: p.Arg2003Cys
Coding: c.6007C>T
MANE Select: NM_001110556
dbSNP: rs2067636406
Type: single nucleotide variant
Location: chrX:154353311 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB

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

Disease context

FLNA-related disorder

Similar variants

FLNA p.Arg2003His Uncertain significance ★ ⚠ same residue
FLNA c.5861-2A>G Pathogenic/Likely pathogenic ★★ same condition
FLNA c.987+1G>A Likely pathogenic ★★ same condition
FLNA p.Gln1182Ter Likely pathogenic ★★ same condition
FLNA p.Glu254Lys Pathogenic/Likely pathogenic ★★ same condition
FLNA p.Pro207Leu Pathogenic/Likely pathogenic ★★ same condition
FLNA p.Arg24Gly Uncertain significance ★★ ⚠ same condition
FLNA p.Asp673Glu 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/flna-p-arg2003cys (accessed [today's date]).

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