Is FLNA p.Val1965= (c.5895C>T) pathogenic?

FLNA p.Val1965= (c.5895C>T) is classified Likely benign in FLNA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-30). Ultra-rare (popmax 0.0118%, eas); Associated with familial thoracic aortic aneurysm and aortic dissection.

What condition is associated with FLNA p.Val1965= (c.5895C>T)?

FLNA p.Val1965= (c.5895C>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.Val1965= (c.5895C>T) in the general population?

FLNA p.Val1965= (c.5895C>T) is ultra-rare (popmax 0.0118%, eas) (gnomAD).

FLNA p.Val1965=

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.5895C>T · rs782692576 · VCV1136621

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0118%, eas)

Conditions

familial thoracic aortic aneurysm and aortic dissection

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.091	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.8	GERP -0.43, phastCons 1
Overall
CADD	11.41	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0118% East Asian · 4/33,809 alleles

Filtering AF 0.00396% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00235%

Overall 0.00132% 16/1,210,432 alleles · ultra-rare exomes 14/1,097,549 · genomes 2/112,883 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0118%	8,452
Remaining individualsnot grpmax-eligible	0.0021%	47,629
South Asian	0.00176%	56,910
African / African-American	0.00174%	57,501
European (non-Finnish)	0.00101%	99,474

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.Val1965=
Coding: c.5895C>T
MANE Select: NM_001110556
dbSNP: rs782692576
Type: single nucleotide variant
Location: chrX:154353423 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 1965: 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

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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-val1965 (accessed [today's date]).

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