Is FLNA p.Pro271fs (c.812del) pathogenic?

FLNA p.Pro271fs (c.812del) is classified Pathogenic in FLNA (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-24). No gnomAD frequency available for this variant; Associated with heterotopia, periventricular, X-linked dominant.

What condition is associated with FLNA p.Pro271fs (c.812del)?

FLNA p.Pro271fs (c.812del) is associated with heterotopia, periventricular, X-linked dominant, otopalatodigital syndrome type 2, Melnick-Needles syndrome (ClinVar).

How common is FLNA p.Pro271fs (c.812del) in the general population?

FLNA p.Pro271fs (c.812del) is no gnomAD frequency available for this variant (gnomAD).

FLNA p.Pro271fs

c.812del · rs2148118964 · VCV1070215

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

heterotopia, periventricular, X-linked dominant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 5 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -16	GERP -1.7

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FLNA
Protein: p.Pro271fs
Coding: c.812del
MANE Select: NM_001110556
dbSNP: rs2148118964
Type: Deletion
Location: chrX:154367453 (GRCh38)
Structure: AlphaFold pLDDT 77.37 · 26 PDB
Residue 271: the 'actin-binding' region; the 'disordered' region

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.Pro271= Likely benign ★ same residue
FLNA p.Arg674fs Pathogenic ★★ same condition
FLNA p.Gln378fs Pathogenic/Likely pathogenic ★★ same condition
FLNA p.Ter2648SerextTer? Pathogenic/Likely pathogenic ★★ same condition
FLNA p.Val2212fs Pathogenic ★★ same condition
FLNA p.Lys531del Uncertain significance ★★ same condition
FLNA p.Ser1747_Pro1750del Uncertain significance ★★ same condition
FLNA c.1065+15del Likely benign ★★ 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-pro271fs (accessed [today's date]).

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