Is HAMP p.Cys72= (c.216C>T) pathogenic?

HAMP p.Cys72= (c.216C>T) is classified Likely benign in HAMP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-11). Very rare (popmax 0.00549%, sas); Associated with hereditary hemochromatosis.

What condition is associated with HAMP p.Cys72= (c.216C>T)?

HAMP p.Cys72= (c.216C>T) is associated with hereditary hemochromatosis (ClinVar).

How common is HAMP p.Cys72= (c.216C>T) in the general population?

HAMP p.Cys72= (c.216C>T) is very rare (popmax 0.00549%, sas) (gnomAD).

HAMP p.Cys72=

c.216C>T · rs763369315 · VCV2726029

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

hereditary hemochromatosis

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 3.2	GERP 0.13, phastCons 1
Overall
CADD	9.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,076 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.000372% 6/1,613,984 alleles · very rare exomes 6/1,461,656 · genomes 0/152,328 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00549%	18,215
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

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: HAMP
Protein: p.Cys72=
Coding: c.216C>T
MANE Select: NM_021175
dbSNP: rs763369315
Type: single nucleotide variant
Location: chr19:35285003 (GRCh38)
Gene constraint: LOEUF 1.464 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.16 · 6 PDB
Residue 72: a disulfide bond

Full HAMP 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

HAMP p.Cys72Ter Uncertain significance ★ same residue
HAMP c.-25G>A Pathogenic/Likely pathogenic ★★ same condition
HAMP p.Arg75Ter Likely pathogenic ★★ same condition
HAMP p.Arg59Gly Uncertain significance ★★ ⚠ same condition
HAMP p.Thr22Ile Uncertain significance ★★ ⚠ same condition
HAMP c.150+7G>C Likely benign ★★ same condition
HAMP p.Cys70= Likely benign ★★ same condition
HAMP p.Gly71Asp Benign/Likely benign ★★ 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/hamp-p-cys72 (accessed [today's date]).

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