Is FTL p.Ala56Pro (c.166G>C) pathogenic?

FTL p.Ala56Pro (c.166G>C) is classified Uncertain significance in FTL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-22). AlphaMissense: likely pathogenic (0.8888); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FTL p.Ala56Pro (c.166G>C)?

FTL p.Ala56Pro (c.166G>C) is associated with Inborn genetic diseases (ClinVar).

How common is FTL p.Ala56Pro (c.166G>C) in the general population?

FTL p.Ala56Pro (c.166G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FTL p.Ala56Pro (c.166G>C)?

AlphaMissense predicts likely pathogenic (score 0.8888) — an in-silico prediction, not a clinical call.

FTL p.Ala56Pro

c.166G>C · VCV3517662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8888 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8888	likely pathogenic
REVEL	0.472	indeterminate
SaProt	LLR -14.63	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	phastCons 1
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

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Ala56Pro
Coding: c.166G>C
MANE Select: NM_000146
Type: single nucleotide variant
Location: chr19:48965833 (GRCh38)
Gene constraint: LOEUF 1.552 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 96.69 · 17 PDB
Residue 56: the ferritin-like diiron domain; an α-helix; the 'catalytic site for iron oxidation' region

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

Similar variants

FTL p.Glu104Ter Pathogenic ★★ same condition
FTL p.Glu164Asp Uncertain significance ★★ ⚠ same condition
FTL p.Gly156Ser Uncertain significance ★★ ⚠ same condition
FTL p.Lys144Met Uncertain significance ★★ same condition
FTL p.Ala99Gly Uncertain significance ★ ⚠ same condition
FTL p.Arg121His Conflicting classifications of pathogenicity ★ ⚠ same condition
FTL p.Asn18Ser Uncertain significance ★ ⚠ same condition
FTL p.Glu138Gly Uncertain significance ★ ⚠ 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-ala56pro (accessed [today's date]).

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