Is FLNA p.Arg7Trp (c.19C>T) pathogenic?

FLNA p.Arg7Trp (c.19C>T) is classified Benign/Likely benign in FLNA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-03). AlphaMissense: ambiguous (0.5111); Ultra-rare (popmax 0.0174%, afr); Associated with Melnick-Needles syndrome.

What condition is associated with FLNA p.Arg7Trp (c.19C>T)?

FLNA p.Arg7Trp (c.19C>T) is associated with Melnick-Needles syndrome, heterotopia, periventricular, X-linked dominant, otopalatodigital syndrome type 2 (ClinVar).

How common is FLNA p.Arg7Trp (c.19C>T) in the general population?

FLNA p.Arg7Trp (c.19C>T) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

What do computational predictors say about FLNA p.Arg7Trp (c.19C>T)?

AlphaMissense predicts ambiguous (score 0.5111) — an in-silico prediction, not a clinical call.

FLNA p.Arg7Trp

c.19C>T · rs941318584 · VCV533576

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5111 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

Conditions

Melnick-Needles syndrome

Computational evidence

Protein change
AlphaMissense	0.5111	ambiguous
REVEL	0.373	indeterminate
SaProt	LLR -8.96	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.12	GERP 0.41
Regional constraint	o/e 2.09	unconstrained · MANE · 79 bp · p 1e-08 · regional, not allelic
Overall
CADD	25.7	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 0.0174% African / African-American · 10/57,581 alleles

Filtering AF 0.00935% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00717%

Overall 0.000833% 10/1,200,246 alleles · ultra-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.Arg7Trp
Coding: c.19C>T
MANE Select: NM_001110556
dbSNP: rs941318584
Type: single nucleotide variant
Location: chrX:154371227 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 7: the 'disordered' region; the 'actin-binding' 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

Similar variants

FLNA p.Arg7Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
FLNA p.Arg7Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
FLNA p.Arg7= Likely 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

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-arg7trp (accessed [today's date]).

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