Is FTL p.Leu78= (c.234C>T) pathogenic?

FTL p.Leu78= (c.234C>T) is classified Benign in FTL (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-15). Rare (popmax 0.322%, sas); Associated with neuroferritinopathy.

What condition is associated with FTL p.Leu78= (c.234C>T)?

FTL p.Leu78= (c.234C>T) is associated with neuroferritinopathy, hereditary hyperferritinemia with congenital cataracts (ClinVar).

How common is FTL p.Leu78= (c.234C>T) in the general population?

FTL p.Leu78= (c.234C>T) is rare (popmax 0.322%, sas) (gnomAD).

How is Neuroferritinopathy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

FTL p.Leu78=

c.234C>T · rs559383814 · VCV893262

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.322%, sas)

Conditions

neuroferritinopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.7
Overall
CADD	7.718	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.322% South Asian · 293/91,072 alleles

Filtering AF 0.291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.28%

Overall 0.019% 306/1,614,170 alleles · rare exomes 292/1,461,804 · genomes 14/152,366 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.322%	311
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.016%	6,251
European (non-Finnish)	0.000169%	589,998

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FTL
Protein: p.Leu78=
Coding: c.234C>T
MANE Select: NM_000146
dbSNP: rs559383814
Type: single nucleotide variant
Location: chr19:48965901 (GRCh38)
Gene constraint: LOEUF 1.552 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 96.69 · 17 PDB
Residue 78: the ferritin-like diiron domain

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

Disease context

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

Also linked: hereditary hyperferritinemia with congenital cataracts

For Neuroferritinopathy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

FTL p.Leu78Phe Uncertain significance ★ ⚠ same residue
FTL p.Leu78Val Uncertain significance ★ ⚠ same residue
FTL c.-149G>C Pathogenic/Likely pathogenic ★★ same condition
FTL c.-150C>A Pathogenic/Likely pathogenic ★★ same condition
FTL c.-157G>A Pathogenic/Likely pathogenic ★★ same condition
FTL c.-160A>G Pathogenic ★★ same condition
FTL c.-161C>T Pathogenic/Likely pathogenic ★★ same condition
FTL c.-164C>A Pathogenic/Likely pathogenic ★★ 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-leu78 (accessed [today's date]).

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