Is ANK1 p.His178fs (c.533del) pathogenic?

ANK1 p.His178fs (c.533del) is classified Likely pathogenic in ANK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-04). Absent from gnomAD.

How common is ANK1 p.His178fs (c.533del) in the general population?

ANK1 p.His178fs (c.533del) is absent from gnomAD (gnomAD).

ANK1 p.His178fs

c.533del · rs2486987534 · VCV2683401

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 in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 6 of 43
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 2.1, phastCons 1

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.His178fs
Coding: c.533del
MANE Select: NM_000037
dbSNP: rs2486987534
Type: Deletion
Location: chr8:41725840 (GRCh38)
Gene constraint: LOEUF 0.299 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.64 · 21 PDB
Residue 178: an α-helix; the '89 kda domain' region

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

Similar variants

ANK1 p.His178Tyr Uncertain significance ★ same residue
ANK1 p.Ala1605fs Likely pathogenic ★★ same type
ANK1 p.Ala461fs Likely pathogenic ★★ same type
ANK1 p.Ala983fs Pathogenic ★★ same type
ANK1 p.Arg1137fs Pathogenic/Likely pathogenic ★★ same type
ANK1 p.Arg1377fs Pathogenic/Likely pathogenic ★★ same type
ANK1 p.Asn756fs Likely pathogenic ★★ same type
ANK1 p.Cys1216_Pro1217insTer 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/ank1-p-his178fs (accessed [today's date]).

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