Is FTH1 p.Ala19= (c.57C>T) pathogenic?

FTH1 p.Ala19= (c.57C>T) is classified Likely benign in FTH1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-14). Ultra-rare (popmax 0.0723%, afr).

How common is FTH1 p.Ala19= (c.57C>T) in the general population?

FTH1 p.Ala19= (c.57C>T) is ultra-rare (popmax 0.0723%, afr) (gnomAD).

FTH1 p.Ala19=

c.57C>T · rs370105090 · VCV3032123

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0723%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP -2.2, phastCons 1
Overall
CADD	15.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0723% African / African-American · 54/74,638 alleles

Filtering AF 0.0569% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0513%

Overall 0.0046% 74/1,607,252 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0723%	1,382
Admixed American	0.00669%	14,953
Remaining individualsnot grpmax-eligible	0.00322%	31,024
European (non-Finnish)	0.00119%	84,086

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.Ala19=
Coding: c.57C>T
MANE Select: NM_002032
dbSNP: rs370105090
Type: single nucleotide variant
Location: chr11:61967369 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 95.69 · 167 PDB
Residue 19: an α-helix; the ferritin-like diiron domain

Full FTH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BEST1 p.Arg218Ser Likely pathogenic ★★ same type
BEST1 p.Val311Gly Pathogenic/Likely pathogenic ★★ same type
FTH1 c.*312A>G Uncertain significance ★★ same type
FTH1 c.-136C>A Uncertain significance ★ same type
FTH1 c.-14C>T Uncertain significance ★ same type
FTH1 c.-2C>T Uncertain significance ★ same type
FTH1 p.Asp172Asn Uncertain significance ★ ⚠ same type
FTH1 p.Leu149Val Uncertain significance ★ 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/fth1-p-ala19 (accessed [today's date]).

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