Is HBB p.His144= (c.432C>T) pathogenic?

HBB p.His144= (c.432C>T) is classified Benign/Likely benign in HBB (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-28). Rare (popmax 0.484%, afr); Associated with Inborn genetic diseases.

What condition is associated with HBB p.His144= (c.432C>T)?

HBB p.His144= (c.432C>T) is associated with Inborn genetic diseases, beta thalassemia (ClinVar).

How common is HBB p.His144= (c.432C>T) in the general population?

HBB p.His144= (c.432C>T) is rare (popmax 0.484%, afr) (gnomAD).

HBB p.His144=

c.432C>T · rs36020563 · VCV36329

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.484%, afr)

Conditions

Inborn genetic diseases

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 1, phastCons 1
Overall
CADD	6.892	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.484% African / African-American · 363/75,044 alleles

Filtering AF 0.443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.427%

Overall 0.0288% 465/1,614,142 alleles · rare exomes 268/1,461,826 · genomes 197/152,316 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.484%	207
Remaining individualsnot grpmax-eligible	0.0336%	2,976
Middle Eastern	0.033%	3,031
Admixed American	0.03%	3,335
European (non-Finnish)	0.00492%	20,345
South Asian	0.00329%	30,360

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: HBB
Protein: p.His144=
Coding: c.432C>T
MANE Select: NM_000518
dbSNP: rs36020563
Type: single nucleotide variant
Location: chr11:5225610 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 144: a binding site; a UniProt-annotated variant site (in rancho mirage); a UniProt-annotated variant site (in syracuse; o(2) affinity up); a UniProt-annotated variant site (in little rock; o(2) affinity up); a UniProt-annotated variant site (in abruzzo; o(2) affinity up); an α-helix; the globin domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: beta thalassemia

Similar variants

HBB p.His144Arg Pathogenic/Likely pathogenic ★★ ⚠ same residue
HBB p.His144Tyr Likely benign ★★ ⚠ same residue
HBB p.His144Pro Pathogenic ★ same residue
HBB c.316-146T>G Pathogenic ★★★ same condition
HBB c.316-197C>T Pathogenic ★★★ same condition
HBB c.92+5G>C Pathogenic ★★★ same condition
HBB c.-78A>C Pathogenic ★★★ same condition
HBB c.*111A>G 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/hbb-p-his144 (accessed [today's date]).

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