Is FLNA p.Pro480Ser (c.1438C>T) pathogenic?

FLNA p.Pro480Ser (c.1438C>T) is classified Uncertain significance in FLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-21). AlphaMissense: likely benign (0.3266); Absent from gnomAD v4.1; Associated with heterotopia, periventricular, X-linked dominant.

What condition is associated with FLNA p.Pro480Ser (c.1438C>T)?

FLNA p.Pro480Ser (c.1438C>T) is associated with heterotopia, periventricular, X-linked dominant, otopalatodigital syndrome type 2, Melnick-Needles syndrome (ClinVar).

How common is FLNA p.Pro480Ser (c.1438C>T) in the general population?

FLNA p.Pro480Ser (c.1438C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLNA p.Pro480Ser (c.1438C>T)?

AlphaMissense predicts likely benign (score 0.3266) — an in-silico prediction, not a clinical call.

FLNA p.Pro480Ser

c.1438C>T · rs782682232 · VCV565416

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3266 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

heterotopia, periventricular, X-linked dominant

Computational evidence

Protein change
AlphaMissense	0.3266	likely benign
REVEL	0.656	pathogenic-leaning
SaProt	LLR -8.96	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 6,571 bp · p 2.7e-08 · regional, not allelic
Overall
CADD	23.4	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

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.Pro480Ser
Coding: c.1438C>T
MANE Select: NM_001110556
dbSNP: rs782682232
Type: single nucleotide variant
Location: chrX:154365478 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 480: an α-helix

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

Disease context

heterotopia, periventricular, X-linked dominant — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: otopalatodigital syndrome type 2 Melnick-Needles syndrome frontometaphyseal dysplasia

Similar variants

FLNA p.Pro480= Likely benign ★★ same residue
FLNA p.Pro480Gln Uncertain significance ★ ⚠ same residue
FLNA p.Pro480Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
FLNA p.Pro480Thr Uncertain significance ★ ⚠ 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-pro480ser (accessed [today's date]).

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