Is HBB p.His3fs (c.8del) pathogenic?

HBB p.His3fs (c.8del) is classified Pathogenic/Likely pathogenic in HBB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-06). No gnomAD frequency available for this variant; Associated with hemoglobinopathy.

What condition is associated with HBB p.His3fs (c.8del)?

HBB p.His3fs (c.8del) is associated with hemoglobinopathy, beta thalassemia (ClinVar).

How common is HBB p.His3fs (c.8del) in the general population?

HBB p.His3fs (c.8del) is no gnomAD frequency available for this variant (gnomAD).

HBB p.His3fs

c.8del · rs1847589398 · VCV869242

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hemoglobinopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.43	GERP -3.7

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: HBB
Protein: p.His3fs
Coding: c.8del
MANE Select: NM_000518
dbSNP: rs1847589398
Type: Deletion
Location: chr11:5227014 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 3: an α-helix; the globin domain; a UniProt-annotated variant site (in graz); a UniProt-annotated variant site (in okayama; o(2) affinity up); a UniProt-annotated variant site (in deer lodge; o(2) affinity up); a UniProt-annotated variant site (in fukuoka); a binding site

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

Disease context

hemoglobinopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: beta thalassemia

Similar variants

HBB p.His3= Benign ★★ same residue
HBB p.His3_Pro6delinsProGluValLysSerAlaTer Pathogenic same residue
HBB c.315+2del Pathogenic/Likely pathogenic ★★ same condition
HBB c.93-22_95del Pathogenic ★★ same condition
HBB c.*110_*111del Pathogenic/Likely pathogenic ★★ same condition
HBB c.*110_*114del Pathogenic/Likely pathogenic ★★ same condition
HBB p.Glu23fs Pathogenic/Likely pathogenic ★★ same condition
HBB p.Glu7fs 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-his3fs (accessed [today's date]).

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