Is HBB p.Ala141Ile (c.421_422delinsAT) pathogenic?

HBB p.Ala141Ile (c.421422delinsAT) is classified Uncertain significance in HBB (ClinVar, Single submitter, 1 submitter). No gnomAD frequency available for this variant; Associated with erythrocytosis, familial, 6.

What condition is associated with HBB p.Ala141Ile (c.421_422delinsAT)?

HBB p.Ala141Ile (c.421_422delinsAT) is associated with erythrocytosis, familial, 6 (ClinVar).

How common is HBB p.Ala141Ile (c.421_422delinsAT) in the general population?

HBB p.Ala141Ile (c.421_422delinsAT) is no gnomAD frequency available for this variant (gnomAD).

HBB p.Ala141Ile

c.421_422delinsAT · rs2494291897 · VCV2585253

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

erythrocytosis, familial, 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.4	GERP 1, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 1,420 bp · p 0.11 · regional, not allelic

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.Ala141Ile
Coding: c.421_422delinsAT
MANE Select: NM_000518
dbSNP: rs2494291897
Type: Indel
Location: chr11:5225620 (GRCh38)
Gene constraint: LOEUF 1.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 350 PDB
Residue 141: a UniProt-annotated variant site (in himeji; unstable; o(2) affinity down); a UniProt-annotated variant site (in st jacques; o(2) affinity up); a UniProt-annotated variant site (in puttelange; polycythemia; o(2) affinity up); 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

Disease context

erythrocytosis, familial, 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

HBB p.Ala141Val Pathogenic ★ ⚠ same residue
HBB p.Ala141Asp Uncertain significance ★ ⚠ same residue
HBB c.316-197C>T Pathogenic ★★★ same condition
HBB c.92+5G>C Pathogenic ★★★ same condition
HBB c.-78A>C Pathogenic ★★★ same condition
HBB p.Ala28Ser Pathogenic ★★★ ⚠ same condition
HBB p.Lys18Ter Pathogenic ★★★ same condition
HBB c.-75G>C Uncertain significance ★★★ 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-ala141ile (accessed [today's date]).

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