Is HBB p.Ala130fs (c.389_401del) pathogenic?

HBB p.Ala130fs (c.389401del) is classified Likely pathogenic in HBB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-13). No gnomAD frequency available for this variant.

How common is HBB p.Ala130fs (c.389_401del) in the general population?

HBB p.Ala130fs (c.389_401del) is no gnomAD frequency available for this variant (gnomAD).

HBB p.Ala130fs

c.389_401del · rs2494292050 · VCV1705956

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

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 -0.027	GERP 1, phastCons 0.001

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.Ala130fs
Coding: c.389_401del
MANE Select: NM_000518
dbSNP: rs2494292050
Type: Deletion
Location: chr11:5225641 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 130: a UniProt-annotated variant site (in crete; o(2) affinity up; unstable); a UniProt-annotated variant site (in la desirade; o(2) affinity down; unstable); a functional site ((microbial infection) cleavage; by n.americanus apr-2); an α-helix; the globin domain

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

Similar variants

HBB p.Ala130del Uncertain significance ★ same residue
HBB p.Ala130Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
HBB p.Ala130Thr Uncertain significance ★ ⚠ same residue
HBB p.Ala130Val Conflicting classifications of pathogenicity ★ ⚠ same residue
HBB c.315+2del Pathogenic/Likely pathogenic ★★ same type
HBB c.93-22_95del Pathogenic ★★ same type
HBB c.*110_*111del Pathogenic/Likely pathogenic ★★ same type
HBB c.*110_*114del Pathogenic/Likely pathogenic ★★ same type

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-ala130fs (accessed [today's date]).

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