Is FLNA p.Asp2096= (c.6288C>T) pathogenic?

FLNA p.Asp2096= (c.6288C>T) is classified Benign/Likely benign in FLNA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-01). Very rare (popmax 0.00257%, nfe); Associated with Melnick-Needles syndrome.

What condition is associated with FLNA p.Asp2096= (c.6288C>T)?

FLNA p.Asp2096= (c.6288C>T) is associated with Melnick-Needles syndrome, heterotopia, periventricular, X-linked dominant, otopalatodigital syndrome type 2 (ClinVar).

How common is FLNA p.Asp2096= (c.6288C>T) in the general population?

FLNA p.Asp2096= (c.6288C>T) is very rare (popmax 0.00257%, nfe) (gnomAD).

FLNA p.Asp2096=

c.6288C>T · rs782376124 · VCV516268

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00257%, nfe)

Conditions

Melnick-Needles syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.8, phastCons 0.99
Overall
CADD	8.823	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00257% European (non-Finnish) · 23/895,072 alleles

Filtering AF 0.00171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00143%

Overall 0.0019% 23/1,210,375 alleles · very rare

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.Asp2096=
Coding: c.6288C>T
MANE Select: NM_001110556
dbSNP: rs782376124
Type: single nucleotide variant
Location: chrX:154352863 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 2096: a β-strand

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

Disease context

Melnick-Needles syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: heterotopia, periventricular, X-linked dominant otopalatodigital syndrome type 2 frontometaphyseal dysplasia familial thoracic aortic aneurysm and aortic dissection

Similar variants

FLNA p.Asp2096Asn Conflicting classifications of pathogenicity ★ ⚠ 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
FLNA p.Ala1188Thr 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/flna-p-asp2096 (accessed [today's date]).

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