Is FLNA p.Pro1348Ser (c.4042C>T) pathogenic?

FLNA p.Pro1348Ser (c.4042C>T) is classified Uncertain significance in FLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-23). AlphaMissense: likely benign (0.12); Absent from gnomAD v4.1.

How common is FLNA p.Pro1348Ser (c.4042C>T) in the general population?

FLNA p.Pro1348Ser (c.4042C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FLNA p.Pro1348Ser (c.4042C>T)?

AlphaMissense predicts likely benign (score 0.12) — an in-silico prediction, not a clinical call.

FLNA p.Pro1348Ser

c.4042C>T · rs782628781 · VCV1334522

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.12 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.12	likely benign
REVEL	0.362	indeterminate
SaProt	LLR -6.92	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 -2.2	GERP -0.67
Regional constraint	o/e 0.74	unconstrained · MANE · 11 kb · p 3.1e-20 · regional, not allelic
Overall
CADD	19.7	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

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.Pro1348Ser
Coding: c.4042C>T
MANE Select: NM_001110556
dbSNP: rs782628781
Type: single nucleotide variant
Location: chrX:154359584 (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.Pro1348= Benign/Likely benign ★★ same residue
FLNA p.Pro1348Leu 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
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-pro1348ser (accessed [today's date]).

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