Is FLNA p.Arg24Pro (c.71G>C) pathogenic?

FLNA p.Arg24Pro (c.71G>C) is classified Uncertain significance in FLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-18). AlphaMissense: likely benign (0.1196); Very rare (popmax 0.000113%, nfe); Associated with Melnick-Needles syndrome.

What condition is associated with FLNA p.Arg24Pro (c.71G>C)?

FLNA p.Arg24Pro (c.71G>C) is associated with Melnick-Needles syndrome, heterotopia, periventricular, X-linked dominant, otopalatodigital syndrome type 2 (ClinVar).

How common is FLNA p.Arg24Pro (c.71G>C) in the general population?

FLNA p.Arg24Pro (c.71G>C) is very rare (popmax 0.000113%, nfe) (gnomAD).

What do computational predictors say about FLNA p.Arg24Pro (c.71G>C)?

AlphaMissense predicts likely benign (score 0.1196) — an in-silico prediction, not a clinical call.

FLNA p.Arg24Pro

c.71G>C · VCV3757632

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1196 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000113%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Melnick-Needles syndrome

Computational evidence

Protein change
AlphaMissense	0.1196	likely benign
REVEL	0.351	indeterminate
SaProt	LLR -6.07	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.31, phastCons 0.33
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

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000113% European (non-Finnish) · 1/887,288 alleles

Overall 8.38e-05% 1/1,193,946 alleles · very rare exomes 1/1,081,026 · genomes 0/112,920 · 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.Arg24Pro
Coding: c.71G>C
MANE Select: NM_001110556
Type: single nucleotide variant
Location: chrX:154371175 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 24: 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.Arg24Gly Uncertain significance ★★ ⚠ same residue
FLNA p.Arg24Trp Uncertain significance ★★ ⚠ same residue
FLNA p.Arg24= Likely benign ★★ same residue
FLNA p.Arg24Leu 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

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-arg24pro (accessed [today's date]).

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