Is FTL p.Leu112fs (c.335del) pathogenic?

FTL p.Leu112fs (c.335del) is classified Likely pathogenic in FTL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-13). Associated with L-ferritin deficiency.

What condition is associated with FTL p.Leu112fs (c.335del)?

FTL p.Leu112fs (c.335del) is associated with L-ferritin deficiency (ClinVar).

FTL p.Leu112fs

c.335del · VCV4845668

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

L-ferritin deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (3 of 4, 43 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.5	phastCons 0.99

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

Variant & gene context

Gene: FTL
Protein: p.Leu112fs
Coding: c.335del
MANE Select: NM_000146
Type: Deletion
Location: chr19:48966363 (GRCh38)
Gene constraint: LOEUF 1.552 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 96.69 · 17 PDB
Residue 112: the ferritin-like diiron domain; an α-helix

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

Disease context

L-ferritin deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FTL p.Leu112Ser Uncertain significance ★ ⚠ same residue
FTL p.Leu112= Likely benign ★ same residue
FTL c.-149G>C Pathogenic/Likely pathogenic ★★ same condition
FTL c.-161C>T Pathogenic/Likely pathogenic ★★ same condition
FTL p.Glu104Ter Pathogenic ★★ same condition
FTL p.Leu55= Benign ★★ same condition
FTL p.Met1Arg Uncertain significance ★ same condition
FTL p.Met1Val Conflicting classifications of pathogenicity ★ 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/ftl-p-leu112fs (accessed [today's date]).

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