Is FTL p.Ala16Asp (c.47C>A) pathogenic?

FTL p.Ala16Asp (c.47C>A) is classified Uncertain significance in FTL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-14). AlphaMissense: ambiguous (0.5369); Absent from gnomAD v4.1; Associated with hereditary hyperferritinemia with congenital cataracts.

How common is FTL p.Ala16Asp (c.47C>A) in the general population?

FTL p.Ala16Asp (c.47C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FTL p.Ala16Asp (c.47C>A)?

AlphaMissense predicts ambiguous (score 0.5369) — an in-silico prediction, not a clinical call.

FTL p.Ala16Asp

Q: What condition is associated with FTL p.Ala16Asp (c.47C>A)?

FTL p.Ala16Asp (c.47C>A) is associated with hereditary hyperferritinemia with congenital cataracts, neuroferritinopathy (ClinVar).

Q: How is Hereditary hyperferritinemia-cataract syndrome inherited?

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

c.47C>A · VCV3755302

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5369 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary hyperferritinemia with congenital cataracts

Computational evidence

Protein change
AlphaMissense	0.5369	ambiguous
REVEL	0.377	indeterminate
SaProt	LLR -12.53	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.65	phastCons 0.14
Regional constraint	o/e 0.82	unconstrained · MANE · 1,224 bp · p 0.0076 · regional, not allelic
Overall
CADD	23.3	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.Ala16Asp
Coding: c.47C>A
MANE Select: NM_000146
Type: single nucleotide variant
Location: chr19:48965554 (GRCh38)
Gene constraint: LOEUF 1.552 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 96.69 · 17 PDB
Residue 16: an α-helix; the ferritin-like diiron domain

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

Disease context

hereditary hyperferritinemia with congenital cataracts — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuroferritinopathy

For Hereditary hyperferritinemia-cataract syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages

Similar variants

FTL p.Ala16= Likely benign ★★ same residue
FTL p.Ala16Val 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-ala16asp (accessed [today's date]).

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