Is HFE p.Asp255fs (c.762del) pathogenic?

HFE p.Asp255fs (c.762del) is classified Pathogenic in HFE (ClinVar, Single submitter, 1 submitter; last evaluated 2017-11-16). No gnomAD frequency available for this variant; Associated with hereditary hemochromatosis.

What condition is associated with HFE p.Asp255fs (c.762del)?

HFE p.Asp255fs (c.762del) is associated with hereditary hemochromatosis (ClinVar).

How common is HFE p.Asp255fs (c.762del) in the general population?

HFE p.Asp255fs (c.762del) is no gnomAD frequency available for this variant (gnomAD).

HFE p.Asp255fs

c.762del · rs1554154042 · VCV530393

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary hemochromatosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.8

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: HFE
Protein: p.Asp255fs
Coding: c.762del
MANE Select: NM_000410
dbSNP: rs1554154042
Type: Deletion
Location: chr6:26092828 (GRCh38)
Gene constraint: LOEUF 1.037 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.62 · 2 PDB
Residue 255: the ig-like c1-type domain; a β-strand; the 'alpha-3' region

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

Disease context

hereditary hemochromatosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

HFE p.Asp255= Likely benign ★ same residue
HFE p.His341fs Pathogenic ★★ same condition
HFE p.Leu183fs Pathogenic/Likely pathogenic ★★ same condition
HFE p.Trp94fs Pathogenic/Likely pathogenic ★★ same condition
HFE c.1006+19del Benign/Likely benign ★★ same condition
HFE p.Arg161fs Pathogenic ★ same condition
HFE p.Asn259fs Pathogenic ★ same condition
HFE p.Glu147fs Pathogenic ★ 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/hfe-p-asp255fs (accessed [today's date]).

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