Is HAMP p.Ala47= (c.141C>T) pathogenic?

HAMP p.Ala47= (c.141C>T) is classified Likely benign in HAMP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-25). Very rare (popmax 0.00223%, eas); Associated with hereditary hemochromatosis.

What condition is associated with HAMP p.Ala47= (c.141C>T)?

HAMP p.Ala47= (c.141C>T) is associated with hereditary hemochromatosis (ClinVar).

How common is HAMP p.Ala47= (c.141C>T) in the general population?

HAMP p.Ala47= (c.141C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

HAMP p.Ala47=

c.141C>T · rs2513558617 · VCV2893395

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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
Pangolin	Δ0.20	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -3.2	GERP -2.5
Overall
CADD	1.295	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,878 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,586 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,878
European (non-Finnish)	0.00017%	589,866

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.Ala47=
Coding: c.141C>T
MANE Select: NM_021175
dbSNP: rs2513558617
Type: single nucleotide variant
Location: chr19:35284839 (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-ala47 (accessed [today's date]).

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