Is HAMP p.Ala9= (c.27C>G) pathogenic?

HAMP p.Ala9= (c.27C>G) is classified Likely benign in HAMP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-21). Very rare (popmax 0.00329%, sas); Associated with hereditary hemochromatosis.

What condition is associated with HAMP p.Ala9= (c.27C>G)?

HAMP p.Ala9= (c.27C>G) is associated with hereditary hemochromatosis (ClinVar).

How common is HAMP p.Ala9= (c.27C>G) in the general population?

HAMP p.Ala9= (c.27C>G) is very rare (popmax 0.00329%, sas) (gnomAD).

HAMP p.Ala9=

c.27C>G · rs201371612 · VCV1623708

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, 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 -3.7	GERP -4.5
Overall
CADD	0.718	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,088 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00142% 23/1,614,124 alleles · very rare exomes 23/1,461,794 · genomes 0/152,330 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,363
European (non-Finnish)	0.00161%	62,106
Remaining individualsnot grpmax-eligible	0.0016%	62,504

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.Ala9=
Coding: c.27C>G
MANE Select: NM_021175
dbSNP: rs201371612
Type: single nucleotide variant
Location: chr19:35282604 (GRCh38)
Gene constraint: LOEUF 1.464 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.16 · 6 PDB

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 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
HAMP c.150+6C>T Uncertain significance ★ 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-ala9 (accessed [today's date]).

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