Is HBB p.Phe43fs (c.126dup) pathogenic?

HBB p.Phe43fs (c.126dup) is classified Likely pathogenic in HBB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-11). No gnomAD frequency available for this variant; Associated with hemoglobinopathy.

What condition is associated with HBB p.Phe43fs (c.126dup)?

HBB p.Phe43fs (c.126dup) is associated with hemoglobinopathy (ClinVar).

How common is HBB p.Phe43fs (c.126dup) in the general population?

HBB p.Phe43fs (c.126dup) is no gnomAD frequency available for this variant (gnomAD).

HBB p.Phe43fs

c.126dup · rs2133588679 · VCV1098798

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 2 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	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.Phe43fs
Coding: c.126dup
MANE Select: NM_000518
dbSNP: rs2133588679
Type: Duplication
Location: chr11:5226765 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 43: a UniProt-annotated variant site (in louisville; unstable); a UniProt-annotated variant site (in hammersmith); a UniProt-annotated variant site (in bruxelles); the globin domain

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

Similar variants

HBB p.Phe43del Conflicting classifications of pathogenicity ★ same residue
HBB p.Glu44Ter Pathogenic ★★ same condition
HBB p.Leu29fs Pathogenic ★★ same condition
HBB p.Phe43Ser Pathogenic ★★ same residue
HBB p.Trp16fs Pathogenic ★★ same condition
HBB p.Val99fs Pathogenic/Likely pathogenic ★★ same condition
HBB p.Arg41fs Pathogenic ★ same condition
HBB p.His117fs 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-phe43fs (accessed [today's date]).

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