Is FLNA p.Arg2598= (c.7794G>A) pathogenic?

FLNA p.Arg2598= (c.7794G>A) is classified Conflicting classifications of pathogenicity in FLNA (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-05-01). Very rare (popmax 0.00123%, nfe); Associated with Melnick-Needles syndrome.

What condition is associated with FLNA p.Arg2598= (c.7794G>A)?

FLNA p.Arg2598= (c.7794G>A) is associated with Melnick-Needles syndrome, heterotopia, periventricular, X-linked dominant, otopalatodigital syndrome type 2 (ClinVar).

How common is FLNA p.Arg2598= (c.7794G>A) in the general population?

FLNA p.Arg2598= (c.7794G>A) is very rare (popmax 0.00123%, nfe) (gnomAD).

FLNA p.Arg2598=

c.7794G>A · rs782372740 · VCV197562

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00123%, 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 -0.24	GERP -3.7
Overall
CADD	9.356	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00123% European (non-Finnish) · 11/895,280 alleles

Filtering AF 0.000659% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000482%

Overall 0.000908% 11/1,211,253 alleles · very rare exomes 11/1,097,353 · genomes 0/113,900 · joint denominator

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.Arg2598=
Coding: c.7794G>A
MANE Select: NM_001110556
dbSNP: rs782372740
Type: single nucleotide variant
Location: chrX:154348999 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 2598: a β-strand; the 'self-association site, tail' region

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 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
FLNA p.Arg1515Ter 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-arg2598 (accessed [today's date]).

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