Is HBB p.Glu23fs (c.68_74del) pathogenic?

HBB p.Glu23fs (c.6874del) is classified Pathogenic/Likely pathogenic in HBB (ClinVar, Multiple submitters, 7 submitters; last evaluated 2024-06-25). No gnomAD frequency available for this variant; Associated with HBB-related disorder.

What condition is associated with HBB p.Glu23fs (c.68_74del)?

HBB p.Glu23fs (c.68_74del) is associated with HBB-related disorder, beta thalassemia (ClinVar).

How common is HBB p.Glu23fs (c.68_74del) in the general population?

HBB p.Glu23fs (c.68_74del) is no gnomAD frequency available for this variant (gnomAD).

HBB p.Glu23fs

c.68_74del · rs281864898 · VCV869360

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

HBB-related disorder

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 -1.4	GERP 1.9

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.Glu23fs
Coding: c.68_74del
MANE Select: NM_000518
dbSNP: rs281864898
Type: Deletion
Location: chr11:5226948 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 23: an α-helix; the globin domain; a UniProt-annotated variant site (in g-coushatta/g-saskatoon/g-taegu/hsin chu); a UniProt-annotated variant site (in g-taipei); a UniProt-annotated variant site (in e-saskatoon); a UniProt-annotated variant site (in d-iran); a UniProt-annotated variant site (in d-granada)

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

Disease context

Also linked: beta thalassemia

Similar variants

HBB p.Glu23Ter Pathogenic ★★ same residue
HBB p.Glu23Ala Conflicting classifications of pathogenicity ★ ⚠ 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.Glu7fs Pathogenic ★★ same condition
HBB p.Gly70fs Pathogenic/Likely 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-glu23fs (accessed [today's date]).

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