Is HBB p.Ser50fs (c.147del) pathogenic?

HBB p.Ser50fs (c.147del) is classified Likely pathogenic in HBB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-11-29). No gnomAD frequency available for this variant; Associated with beta-thalassemia HBB/LCRB.

What condition is associated with HBB p.Ser50fs (c.147del)?

HBB p.Ser50fs (c.147del) is associated with beta-thalassemia HBB/LCRB (ClinVar).

How common is HBB p.Ser50fs (c.147del) in the general population?

HBB p.Ser50fs (c.147del) is no gnomAD frequency available for this variant (gnomAD).

HBB p.Ser50fs

c.147del · rs1554917947 · VCV555215

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

beta-thalassemia HBB/LCRB

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 2 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.8	GERP 1.9, phastCons 1

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.Ser50fs
Coding: c.147del
MANE Select: NM_000518
dbSNP: rs1554917947
Type: Deletion
Location: chr11:5226745 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 50: a UniProt-annotated variant site (in las palmas; slightly unstable); the globin domain

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

Disease context

beta-thalassemia HBB/LCRB — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

HBB c.93-22_95del Pathogenic ★★ same condition
HBB p.Glu7fs Pathogenic ★★ same condition
HBB p.Gly84fs Pathogenic ★★ same condition
HBB p.His78fs Likely pathogenic ★★ same condition
HBB p.Lys18fs Pathogenic ★★ same condition
HBB p.Lys9fs Pathogenic ★★ same condition
HBB p.Phe42fs Pathogenic/Likely pathogenic ★★ same condition
HBB p.Phe46fs 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-ser50fs (accessed [today's date]).

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