Is FTL p.Lys84Arg (c.251A>G) pathogenic?

FTL p.Lys84Arg (c.251A>G) is classified Uncertain significance in FTL (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-15). AlphaMissense: likely benign (0.1442); Absent from gnomAD v4.1; Associated with neuroferritinopathy.

What condition is associated with FTL p.Lys84Arg (c.251A>G)?

FTL p.Lys84Arg (c.251A>G) is associated with neuroferritinopathy, hereditary hyperferritinemia with congenital cataracts (ClinVar).

How common is FTL p.Lys84Arg (c.251A>G) in the general population?

FTL p.Lys84Arg (c.251A>G) is absent from gnomAD v4.1 (gnomAD).

How is Neuroferritinopathy inherited?

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

What do computational predictors say about FTL p.Lys84Arg (c.251A>G)?

AlphaMissense predicts likely benign (score 0.1442) — an in-silico prediction, not a clinical call.

FTL p.Lys84Arg

c.251A>G · VCV3750832

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1442 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

neuroferritinopathy

Computational evidence

Protein change
AlphaMissense	0.1442	likely benign
REVEL	0.445	indeterminate
SaProt	LLR -10.29	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.77	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 11	phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 1,224 bp · p 0.0076 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

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: FTL
Protein: p.Lys84Arg
Coding: c.251A>G
MANE Select: NM_000146
Type: single nucleotide variant
Location: chr19:48966282 (GRCh38)
Gene constraint: LOEUF 1.552 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 96.69 · 17 PDB
Residue 84: the ferritin-like diiron domain; an α-helix

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 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
FTL c.-167C>T Pathogenic ★★ same condition
FTL c.-168G>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-lys84arg (accessed [today's date]).

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