Is FTH1 p.Leu83= (c.249T>G) pathogenic?

FTH1 p.Leu83= (c.249T>G) is classified Benign/Likely benign in FTH1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-27). Low-frequency (popmax 1.01%, afr).

How common is FTH1 p.Leu83= (c.249T>G) in the general population?

FTH1 p.Leu83= (c.249T>G) is low-frequency (popmax 1.01%, afr) (gnomAD).

FTH1 p.Leu83=

c.249T>G · rs41453449 · VCV2049826

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.01%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.34	gain · loss 0.00 · independent
Constraint at this position
Conservation	phyloP -1.2	GERP -4.8
Overall
CADD	6.782	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.01% African / African-American · 761/75,024 alleles

Filtering AF 0.955% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.931%

Overall 0.055% 888/1,613,314 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.01%	99
Middle Eastern	0.185%	540
Admixed American	0.0883%	1,132
Remaining individualsnot grpmax-eligible	0.0673%	1,486
European (non-Finnish)	0.00186%	53,637

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.Leu83=
Coding: c.249T>G
MANE Select: NM_004183 · reported on NM_002032
dbSNP: rs41453449
Type: single nucleotide variant
Location: chr11:61965381 (GRCh38)

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

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-leu83 (accessed [today's date]).

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