Is FTH1 p.Ala161Val (c.482C>T) pathogenic?

FTH1 p.Ala161Val (c.482C>T) is classified Uncertain significance in FTH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: ambiguous (0.3496); Very rare (popmax 0.00988%, sas); Associated with Inborn genetic diseases.

What condition is associated with FTH1 p.Ala161Val (c.482C>T)?

FTH1 p.Ala161Val (c.482C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FTH1 p.Ala161Val (c.482C>T) in the general population?

FTH1 p.Ala161Val (c.482C>T) is very rare (popmax 0.00988%, sas) (gnomAD).

What do computational predictors say about FTH1 p.Ala161Val (c.482C>T)?

AlphaMissense predicts ambiguous (score 0.3496) — an in-silico prediction, not a clinical call.

FTH1 p.Ala161Val

c.482C>T · rs11554842 · VCV2518228

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3496 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00988%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3496	ambiguous
REVEL	0.3	indeterminate
SaProt	LLR -11.30	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 2,695 bp · p 1.6e-07 · regional, not allelic
Overall
CADD	24.2	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 0.00988% South Asian · 9/91,074 alleles

Filtering AF 0.00514% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00375%

Overall 0.00244% 39/1,599,974 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00988%	10,119
Remaining individualsnot grpmax-eligible	0.00481%	20,807
African / African-American	0.00267%	37,506
European (non-Finnish)	0.00203%	49,164
Admixed American	0.00167%	60,020

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: FTH1
Protein: p.Ala161Val
Coding: c.482C>T
MANE Select: NM_004183 · reported on NM_002032
dbSNP: rs11554842
Type: single nucleotide variant
Location: chr11:61964797 (GRCh38)

Full FTH1 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

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/fth1-p-ala161val (accessed [today's date]).

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