Is HJV p.Pro371= (c.1113C>T) pathogenic?

HJV p.Pro371= (c.1113C>T) is classified Conflicting classifications of pathogenicity in HJV (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-01-08). Absent from gnomAD v4.1; Associated with hemochromatosis type 2A.

What condition is associated with HJV p.Pro371= (c.1113C>T)?

HJV p.Pro371= (c.1113C>T) is associated with hemochromatosis type 2A (ClinVar).

How common is HJV p.Pro371= (c.1113C>T) in the general population?

HJV p.Pro371= (c.1113C>T) is absent from gnomAD v4.1 (gnomAD).

How is HJV or HAMP-related hemochromatosis inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

HJV p.Pro371=

c.1113C>T · rs886045239 · VCV292432

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hemochromatosis type 2A

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 2.4	GERP -2.4, phastCons 1
Overall
CADD	8.288	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: HJV
Protein: p.Pro371=
Coding: c.1113C>T
MANE Select: NM_213653
dbSNP: rs886045239
Type: single nucleotide variant
Location: chr1:146018245 (GRCh38)
Gene constraint: LOEUF 1.148 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 82.87 · 2 PDB

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

Disease context

hemochromatosis type 2A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For HJV or HAMP-related hemochromatosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

HJV p.Arg257Ter Pathogenic/Likely pathogenic ★★ same condition
HJV p.Arg326Ter Pathogenic/Likely pathogenic ★★ same condition
HJV p.Arg385Ter Likely pathogenic ★★ same condition
HJV p.Arg63Ter Pathogenic/Likely pathogenic ★★ same condition
HJV p.Cys80Arg Pathogenic ★★ same condition
HJV p.Cys89Arg Likely pathogenic ★★ same condition
HJV p.Gln277Ter Pathogenic/Likely pathogenic ★★ same condition
HJV p.Gly320Val 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/hjv-p-pro371 (accessed [today's date]).

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