Is FTL p.Val17Ile (c.49G>A) pathogenic?

FTL p.Val17Ile (c.49G>A) is classified Uncertain significance in FTL (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely benign (0.1049); Very rare (popmax 0.00229%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FTL p.Val17Ile (c.49G>A)?

FTL p.Val17Ile (c.49G>A) is associated with Inborn genetic diseases (ClinVar).

How common is FTL p.Val17Ile (c.49G>A) in the general population?

FTL p.Val17Ile (c.49G>A) is very rare (popmax 0.00229%, nfe) (gnomAD).

What do computational predictors say about FTL p.Val17Ile (c.49G>A)?

AlphaMissense predicts likely benign (score 0.1049) — an in-silico prediction, not a clinical call.

FTL p.Val17Ile

c.49G>A · VCV4620413

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1049 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00229%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1049	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -9.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 1,224 bp · p 0.0076 · regional, not allelic
Overall
CADD	19.75	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00229% European (non-Finnish) · 27/1,179,954 alleles

Filtering AF 0.00157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00173% 28/1,613,902 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00229%	43,702
Remaining individualsnot grpmax-eligible	0.0016%	62,474

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.Val17Ile
Coding: c.49G>A
MANE Select: NM_000146
Type: single nucleotide variant
Location: chr19:48965556 (GRCh38)
Gene constraint: LOEUF 1.552 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 96.69 · 17 PDB
Residue 17: an α-helix; the ferritin-like diiron domain

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.Ala56Pro 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

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-val17ile (accessed [today's date]).

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