Is FTL p.Phe52Cys (c.155T>G) pathogenic?

FTL p.Phe52Cys (c.155T>G) is classified Conflicting classifications of pathogenicity in FTL (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-08-19). AlphaMissense: likely pathogenic (0.6873); Ultra-rare (popmax 0.0197%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FTL p.Phe52Cys (c.155T>G)?

FTL p.Phe52Cys (c.155T>G) is associated with Inborn genetic diseases, hereditary hyperferritinemia with congenital cataracts, neuroferritinopathy (ClinVar).

How common is FTL p.Phe52Cys (c.155T>G) in the general population?

FTL p.Phe52Cys (c.155T>G) is ultra-rare (popmax 0.0197%, nfe) (gnomAD).

What do computational predictors say about FTL p.Phe52Cys (c.155T>G)?

AlphaMissense predicts likely pathogenic (score 0.6873) — an in-silico prediction, not a clinical call.

FTL p.Phe52Cys

c.155T>G · rs543242420 · VCV1049905

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.6873 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0197%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6873	likely pathogenic
REVEL	0.768	pathogenic-leaning
SaProt	LLR -11.15	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.8	phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 1,224 bp · p 0.0076 · regional, not allelic
Overall
CADD	28.5	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

Grpmax group 0.0197% European (non-Finnish) · 232/1,180,036 alleles

Filtering AF 0.0176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0168%

Overall 0.0147% 238/1,614,184 alleles · ultra-rare exomes 229/1,461,856 · genomes 9/152,328 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0197%	5,086
Remaining individualsnot grpmax-eligible	0.0096%	10,419

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.Phe52Cys
Coding: c.155T>G
MANE Select: NM_000146
dbSNP: rs543242420
Type: single nucleotide variant
Location: chr19:48965822 (GRCh38)
Gene constraint: LOEUF 1.552 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 96.69 · 17 PDB
Residue 52: the ferritin-like diiron domain; an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary hyperferritinemia with congenital cataracts neuroferritinopathy

Similar variants

FTL p.Phe52= Likely benign ★ 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
FTL c.-167C>T 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-phe52cys (accessed [today's date]).

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