Is FLNA p.Pro2480Ser (c.7438C>T) pathogenic?

FLNA p.Pro2480Ser (c.7438C>T) is classified Uncertain significance in FLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-12). AlphaMissense: likely benign (0.0841); Very rare (popmax 0.000112%, nfe).

How common is FLNA p.Pro2480Ser (c.7438C>T) in the general population?

FLNA p.Pro2480Ser (c.7438C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about FLNA p.Pro2480Ser (c.7438C>T)?

AlphaMissense predicts likely benign (score 0.0841) — an in-silico prediction, not a clinical call.

FLNA p.Pro2480Ser

c.7438C>T · rs1557175373 · VCV1704992

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0841 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0841	likely benign
REVEL	0.224	benign-leaning
SaProt	LLR -7.69	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.5	GERP 0.76, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 11 kb · p 3.1e-20 · regional, not allelic
Overall
CADD	23.2	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 0.000112% European (non-Finnish) · 1/895,220 alleles

Overall 8.26e-05% 1/1,211,311 alleles · very rare exomes 1/1,097,342 · genomes 0/113,969 · 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.Pro2480Ser
Coding: c.7438C>T
MANE Select: NM_001110556
dbSNP: rs1557175373
Type: single nucleotide variant
Location: chrX:154349763 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB

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

Similar variants

FLNA p.Pro2480Leu Uncertain significance ★ ⚠ same residue
FLNA p.Pro2480= Likely benign ★ same residue
FLNA p.Pro2480Gln Uncertain significance ★ same residue
FLNA c.1066-1G>A Pathogenic/Likely pathogenic ★★ same type
FLNA c.2022+1G>A Pathogenic ★★ same type
FLNA c.4598+1G>A Pathogenic/Likely pathogenic ★★ same type
FLNA c.4599-1G>A Pathogenic/Likely pathogenic ★★ same type
FLNA c.5417-2A>G Likely pathogenic ★★ same type

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-pro2480ser (accessed [today's date]).

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