Is FTL p.Ala16Val (c.47C>T) pathogenic?

FTL p.Ala16Val (c.47C>T) is classified Uncertain significance in FTL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: ambiguous (0.4421); Very rare (popmax 0.000593%, nfe).

How common is FTL p.Ala16Val (c.47C>T) in the general population?

FTL p.Ala16Val (c.47C>T) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about FTL p.Ala16Val (c.47C>T)?

AlphaMissense predicts ambiguous (score 0.4421) — an in-silico prediction, not a clinical call.

FTL p.Ala16Val

c.47C>T · rs1310208452 · VCV3068840

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4421 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4421	ambiguous
REVEL	0.328	indeterminate
SaProt	LLR -11.46	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	22.9	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 0.000593% European (non-Finnish) · 7/1,179,942 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,613,926 alleles · very rare exomes 6/1,461,736 · genomes 1/152,190 · joint denominator

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.Ala16Val
Coding: c.47C>T
MANE Select: NM_000146
dbSNP: rs1310208452
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

Similar variants

FTL p.Ala16= Likely benign ★★ same residue
FTL p.Ala16Asp Uncertain significance ★ same residue
FTL c.-149G>C Pathogenic/Likely pathogenic ★★ same type
FTL c.-150C>A Pathogenic/Likely pathogenic ★★ same type
FTL c.-157G>A Pathogenic/Likely pathogenic ★★ same type
FTL c.-160A>G Pathogenic ★★ same type
FTL c.-161C>T Pathogenic/Likely pathogenic ★★ same type
FTL c.-164C>A Pathogenic/Likely pathogenic ★★ same type

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-ala16val (accessed [today's date]).

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