Is ANK1 p.Thr1693fs (c.5076dup) pathogenic?

ANK1 p.Thr1693fs (c.5076dup) is classified Likely pathogenic in ANK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-09). Absent from gnomAD; Associated with hereditary spherocytosis type 1.

What condition is associated with ANK1 p.Thr1693fs (c.5076dup)?

ANK1 p.Thr1693fs (c.5076dup) is associated with hereditary spherocytosis type 1 (ClinVar).

How common is ANK1 p.Thr1693fs (c.5076dup) in the general population?

ANK1 p.Thr1693fs (c.5076dup) is absent from gnomAD (gnomAD).

How is Hereditary spherocytosis inherited?

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

ANK1 p.Thr1693fs

c.5076dup · rs2487635140 · VCV2432318

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

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 38 of 43
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.44	GERP -2.9, phastCons 0.65

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: ANK1
Protein: p.Thr1693fs
Coding: c.5076dup
MANE Select: NM_000037
dbSNP: rs2487635140
Type: Duplication
Location: chr8:41672373 (GRCh38)
Gene constraint: LOEUF 0.299 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.64 · 21 PDB
Residue 1693: the '55 kda regulatory domain' region; the 'disordered' 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.Thr1693Met Uncertain significance ★ ⚠ same residue
ANK1 p.Ala428fs Likely pathogenic ★★ same condition
ANK1 p.Asn497fs Pathogenic/Likely pathogenic ★★ same condition
ANK1 p.Leu131fs Pathogenic ★★ same condition
ANK1 p.Leu573fs Pathogenic/Likely pathogenic ★★ same condition
ANK1 p.Tyr3fs Pathogenic/Likely pathogenic ★★ same condition
ANK1 p.Ala478fs Pathogenic ★ same condition
ANK1 p.Arg21fs 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-thr1693fs (accessed [today's date]).

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