Is FLNA p.Phe2353Ser (c.7058T>C) pathogenic?

FLNA p.Phe2353Ser (c.7058T>C) is classified Pathogenic in FLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-09). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1; Associated with neurodevelopmental disorder.

What condition is associated with FLNA p.Phe2353Ser (c.7058T>C)?

FLNA p.Phe2353Ser (c.7058T>C) is associated with neurodevelopmental disorder (ClinVar).

How common is FLNA p.Phe2353Ser (c.7058T>C) in the general population?

FLNA p.Phe2353Ser (c.7058T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLNA p.Phe2353Ser (c.7058T>C)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

FLNA p.Phe2353Ser

c.7058T>C · rs2148102210 · VCV1321934

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic ✓ concordant with ClinVar · top 1% in FLNA
REVEL	0.934	strongly pathogenic-leaning
SaProt	LLR -16.89	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.20	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 11 kb · p 3.1e-20 · regional, not allelic
Overall
CADD	26.1	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.Phe2353Ser
Coding: c.7058T>C
MANE Select: NM_001110556
dbSNP: rs2148102210
Type: single nucleotide variant
Location: chrX:154351007 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB

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

Disease context

neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FLNA p.Phe2353Leu Uncertain significance ★★ ⚠ same residue
FLNA p.Phe2353fs Likely pathogenic ★ 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
FLNA c.5861-2A>G Pathogenic/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-phe2353ser (accessed [today's date]).

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