Is ANK1 p.Pro114fs (c.341_345del) pathogenic?

ANK1 p.Pro114fs (c.341345del) is classified Likely pathogenic in ANK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-10). Associated with hereditary spherocytosis type 1.

What condition is associated with ANK1 p.Pro114fs (c.341_345del)?

ANK1 p.Pro114fs (c.341_345del) is associated with hereditary spherocytosis type 1 (ClinVar).

How is Hereditary spherocytosis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ANK1 p.Pro114fs

c.341_345del · VCV4685875

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary spherocytosis type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 5 of 43
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1

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

Variant & gene context

Gene: ANK1
Protein: p.Pro114fs
Coding: c.341_345del
MANE Select: NM_000037
Type: Deletion
Location: chr8:41727331 (GRCh38)
Gene constraint: LOEUF 0.299 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.64 · 21 PDB
Residue 114: an α-helix; the '89 kda domain' region

Full ANK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary spherocytosis type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary spherocytosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Germany)

Similar variants

ANK1 p.Pro114Leu Likely pathogenic ★ same residue
ANK1 p.Ala1605fs Likely pathogenic ★★ same condition
ANK1 p.Ala461fs Likely pathogenic ★★ same condition
ANK1 p.Arg1137fs Pathogenic/Likely pathogenic ★★ same condition
ANK1 p.Asn756fs Likely pathogenic ★★ same condition
ANK1 p.Cys1216_Pro1217insTer Pathogenic/Likely pathogenic ★★ same condition
ANK1 p.Gln471fs Likely pathogenic ★★ same condition
ANK1 p.Gly1459fs Pathogenic/Likely 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/ank1-p-pro114fs (accessed [today's date]).

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