Is HBB p.Val2fs (c.4del) pathogenic?

HBB p.Val2fs (c.4del) is classified Pathogenic in HBB (ClinVar, No assertion criteria, 2 submitters; last evaluated 2019-11-25). No allele count reported in gnomAD v4.1 (AN 1,596,986); Associated with Beta zero thalassemia.

What condition is associated with HBB p.Val2fs (c.4del)?

HBB p.Val2fs (c.4del) is associated with Beta zero thalassemia, beta thalassemia (ClinVar).

How common is HBB p.Val2fs (c.4del) in the general population?

HBB p.Val2fs (c.4del) is no allele count reported in gnomAD v4.1 (AN 1,596,986) (gnomAD).

HBB p.Val2fs

c.4del · rs63750475 · VCV15508

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,596,986)

Conditions

Beta zero thalassemia

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 3	GERP 0.65, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,596,986). 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.Val2fs
Coding: c.4del
MANE Select: NM_000518
dbSNP: rs63750475
Type: Deletion
Location: chr11:5227018 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 2: a modified residue (n-acetylvaline); a modified residue (n-pyruvate 2-iminyl-valine; in hb a1b); a binding site; a UniProt-annotated variant site (in raleigh; o(2) affinity down)

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

Disease context

Beta zero thalassemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: beta thalassemia

Similar variants

HBB p.Val2Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
HBB p.Val2Met 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.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-val2fs (accessed [today's date]).

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