Is FLNA p.Arg2201= (c.6603C>G) pathogenic?

FLNA p.Arg2201= (c.6603C>G) is classified Uncertain significance in FLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-01). Absent from gnomAD v4.1; Associated with otopalatodigital syndrome type 2.

What condition is associated with FLNA p.Arg2201= (c.6603C>G)?

FLNA p.Arg2201= (c.6603C>G) is associated with otopalatodigital syndrome type 2, heterotopia, periventricular, X-linked dominant, Melnick-Needles syndrome (ClinVar).

How common is FLNA p.Arg2201= (c.6603C>G) in the general population?

FLNA p.Arg2201= (c.6603C>G) is absent from gnomAD v4.1 (gnomAD).

FLNA p.Arg2201=

c.6603C>G · rs2522720717 · VCV2132510

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

otopalatodigital syndrome type 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.34	donor gain · deltas
Constraint at this position
Conservation	phyloP -0.18	GERP -3.7, phastCons 0.097
Overall
CADD	13.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FLNA
Protein: p.Arg2201=
Coding: c.6603C>G
MANE Select: NM_001110556
dbSNP: rs2522720717
Type: single nucleotide variant
Location: chrX:154352347 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 2201: a β-strand

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

Disease context

otopalatodigital syndrome type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

FLNA p.Arg2201Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
FLNA p.Arg2201His Benign ★ ⚠ 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-arg2201 (accessed [today's date]).

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