Is F2 p.Leu152fs (c.454_457del) pathogenic?

F2 p.Leu152fs (c.454457del) is classified Likely pathogenic in F2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-11). Absent from gnomAD; Associated with F2-related disorder.

What condition is associated with F2 p.Leu152fs (c.454_457del)?

F2 p.Leu152fs (c.454_457del) is associated with F2-related disorder (ClinVar).

How common is F2 p.Leu152fs (c.454_457del) in the general population?

F2 p.Leu152fs (c.454_457del) is absent from gnomAD (gnomAD).

F2 p.Leu152fs

c.454_457del · rs2502824222 · VCV2631315

Likely pathogenic Single submitter

Classification

Likely 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

F2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.9	GERP 0.83, phastCons 1

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: F2
Protein: p.Leu152fs
Coding: c.454_457del
MANE Select: NM_000506
dbSNP: rs2502824222
Type: Deletion
Location: chr11:46723411 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI 0.15 (gnomAD)
Structure: AlphaFold pLDDT 84.37 · 480 PDB
Residue 152: the kringle 1 domain

Full F2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

F2-related disorder

Similar variants

F2 p.Arg431His Likely pathogenic ★ ⚠ same condition
F2 c.1472+3G>C Uncertain significance ★ same condition
F2 p.Gly362Arg Uncertain significance ★ ⚠ same condition
F2 p.Asp308fs Pathogenic ★ same type
F2 p.Val185fs Pathogenic ★ same type
F2 c.1473-3_1473-2del Uncertain significance ★ same type
F2 p.His605fs Conflicting classifications of pathogenicity ★ same type
F2 p.Leu423del Uncertain significance ★ 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/f2-p-leu152fs (accessed [today's date]).

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