Is FLNA p.Arg7Pro (c.20G>C) pathogenic?

FLNA p.Arg7Pro (c.20G>C) is classified Conflicting classifications of pathogenicity in FLNA (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-17). AlphaMissense: likely benign (0.1514); Very rare (popmax 0.0087%, afr); Associated with FLNA-related disorder.

What condition is associated with FLNA p.Arg7Pro (c.20G>C)?

FLNA p.Arg7Pro (c.20G>C) is associated with FLNA-related disorder, heterotopia, periventricular, X-linked dominant, otopalatodigital syndrome type 2 (ClinVar).

How common is FLNA p.Arg7Pro (c.20G>C) in the general population?

FLNA p.Arg7Pro (c.20G>C) is very rare (popmax 0.0087%, afr) (gnomAD).

What do computational predictors say about FLNA p.Arg7Pro (c.20G>C)?

AlphaMissense predicts likely benign (score 0.1514) — an in-silico prediction, not a clinical call.

FLNA p.Arg7Pro

c.20G>C · rs781814342 · VCV638389

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1514 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0087%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

FLNA-related disorder

Computational evidence

Protein change
AlphaMissense	0.1514	likely benign
REVEL	0.468	indeterminate
SaProt	LLR -4.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.006	GERP 0.38
Regional constraint	o/e 2.09	unconstrained · MANE · 79 bp · p 1e-08 · regional, not allelic
Overall
CADD	24.2	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 0.0087% African / African-American · 5/57,458 alleles

Filtering AF 0.00337% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00214%

Overall 0.0015% 18/1,200,008 alleles · very rare exomes 15/1,087,038 · genomes 3/112,970 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0087%	11,492
European (non-Finnish)	0.00146%	68,551

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.Arg7Pro
Coding: c.20G>C
MANE Select: NM_001110556
dbSNP: rs781814342
Type: single nucleotide variant
Location: chrX:154371226 (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

FLNA-related disorder

Also linked: heterotopia, periventricular, X-linked dominant otopalatodigital syndrome type 2 Melnick-Needles syndrome frontometaphyseal dysplasia

Similar variants

FLNA p.Arg7Trp Benign/Likely benign ★★ same residue
FLNA p.Arg7Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
FLNA p.Arg7fs Pathogenic ★ 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

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-arg7pro (accessed [today's date]).

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