Is HBB p.Ala116fs (c.339_345dup) pathogenic?

HBB p.Ala116fs (c.339345dup) is classified Pathogenic in HBB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-25). No gnomAD frequency available for this variant; Associated with beta thalassemia.

What condition is associated with HBB p.Ala116fs (c.339_345dup)?

HBB p.Ala116fs (c.339_345dup) is associated with beta thalassemia (ClinVar).

How common is HBB p.Ala116fs (c.339_345dup) in the general population?

HBB p.Ala116fs (c.339_345dup) is no gnomAD frequency available for this variant (gnomAD).

HBB p.Ala116fs

c.339_345dup · rs281864527 · VCV869279

Pathogenic No assertion criteria

Classification

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

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.064	GERP -0.003, phastCons 0.094

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.Ala116fs
Coding: c.339_345dup
MANE Select: NM_000518
dbSNP: rs281864527
Type: Duplication
Location: chr11:5225696 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 116: a UniProt-annotated variant site (in b-thal; hradec kralove; unstable); a UniProt-annotated variant site (in madrid; unstable); an α-helix; the globin domain

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

Disease context

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

Similar variants

HBB p.Ala116Asp Pathogenic ★★ same residue
HBB p.Ala11fs Pathogenic ★★ same condition
HBB p.Asn109fs Pathogenic ★★ same condition
HBB p.Asp22fs Likely pathogenic ★★ same condition
HBB p.Asp48fs Pathogenic ★★ same condition
HBB p.Glu44Ter Pathogenic ★★ same condition
HBB p.Leu29fs Pathogenic ★★ same condition
HBB p.Leu97fs 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-ala116fs (accessed [today's date]).

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