Is FTL p.Ala16= (c.48C>G) pathogenic?

FTL p.Ala16= (c.48C>G) is classified Likely benign in FTL (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-02-14). Ultra-rare (popmax 0.0107%, afr); Associated with hereditary hyperferritinemia with congenital cataracts.

How common is FTL p.Ala16= (c.48C>G) in the general population?

FTL p.Ala16= (c.48C>G) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

FTL p.Ala16=

Q: What condition is associated with FTL p.Ala16= (c.48C>G)?

FTL p.Ala16= (c.48C>G) 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.48C>G · rs11553246 · VCV3043681

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Conditions

hereditary hyperferritinemia with congenital cataracts

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 -2.3
Overall
CADD	12.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/74,924 alleles

Filtering AF 0.00528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000744% 12/1,613,974 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,365
Remaining individualsnot grpmax-eligible	0.0064%	15,621

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.Ala16=
Coding: c.48C>G
MANE Select: NM_000146
dbSNP: rs11553246
Type: single nucleotide variant
Location: chr19:48965555 (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.Ala16Asp Uncertain significance ★ 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-ala16 (accessed [today's date]).

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