Is FLNA p.Arg2001Trp (c.6001C>T) pathogenic?

FLNA p.Arg2001Trp (c.6001C>T) is classified Benign/Likely benign in FLNA (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.2032); Ultra-rare (popmax 0.0139%, afr); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with FLNA p.Arg2001Trp (c.6001C>T)?

FLNA p.Arg2001Trp (c.6001C>T) is associated with familial thoracic aortic aneurysm and aortic dissection, heterotopia, periventricular, X-linked dominant, otopalatodigital syndrome type 2 (ClinVar).

How common is FLNA p.Arg2001Trp (c.6001C>T) in the general population?

FLNA p.Arg2001Trp (c.6001C>T) is ultra-rare (popmax 0.0139%, afr) (gnomAD).

What do computational predictors say about FLNA p.Arg2001Trp (c.6001C>T)?

AlphaMissense predicts likely benign (score 0.2032) — an in-silico prediction, not a clinical call.

FLNA p.Arg2001Trp

Q: How is Familial thoracic aortic aneurysm and aortic dissection inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.6001C>T · rs782160183 · VCV700137

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.2032 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0139%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

familial thoracic aortic aneurysm and aortic dissection

Computational evidence

Protein change
AlphaMissense	0.2032	likely benign
REVEL	0.34	indeterminate
SaProt	LLR -11.59	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP -0.74, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 11 kb · p 3.1e-20 · regional, not allelic
Overall
CADD	23.0	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

Grpmax group 0.0139% African / African-American · 8/57,535 alleles

Filtering AF 0.00686% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.005%

Overall 0.00429% 52/1,210,734 alleles · ultra-rare exomes 49/1,097,790 · genomes 3/112,944 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0499%	2,005
African / African-Americangrpmax	0.0139%	7,192
Remaining individualsnot grpmax-eligible	0.0084%	11,903
South Asian	0.00351%	28,455
East Asian	0.00296%	33,795
European (non-Finnish)	0.0029%	34,438

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg2001Trp
Coding: c.6001C>T
MANE Select: NM_001110556
dbSNP: rs782160183
Type: single nucleotide variant
Location: chrX:154353317 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 2001: a β-strand

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

Disease context

familial thoracic aortic aneurysm and aortic dissection — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: heterotopia, periventricular, X-linked dominant otopalatodigital syndrome type 2 Melnick-Needles syndrome frontometaphyseal dysplasia

For Familial thoracic aortic aneurysm and aortic dissection (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

FLNA p.Arg2001Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
FLNA p.Arg2001Leu Uncertain significance ★ ⚠ same residue
FLNA c.1066-1G>A Pathogenic/Likely pathogenic ★★ same condition
FLNA c.2022+1G>A Pathogenic ★★ same condition
FLNA c.4598+1G>A Pathogenic/Likely pathogenic ★★ same condition
FLNA c.5417-2A>G Likely pathogenic ★★ same condition
FLNA c.868+1G>A Likely pathogenic ★★ same condition
FLNA c.987+1G>A 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/flna-p-arg2001trp (accessed [today's date]).

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