Is ANK1 p.Leu177fs (c.530del) pathogenic?

ANK1 p.Leu177fs (c.530del) is classified Likely pathogenic in ANK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-13). Absent from gnomAD; Associated with ANK1-related disorder.

What condition is associated with ANK1 p.Leu177fs (c.530del)?

ANK1 p.Leu177fs (c.530del) is associated with ANK1-related disorder (ClinVar).

How common is ANK1 p.Leu177fs (c.530del) in the general population?

ANK1 p.Leu177fs (c.530del) is absent from gnomAD (gnomAD).

ANK1 p.Leu177fs

c.530del · rs2486987573 · VCV2633048

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

ANK1-related disorder

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 0.41	GERP -0.033, phastCons 0.99

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.Leu177fs
Coding: c.530del
MANE Select: NM_000037
dbSNP: rs2486987573
Type: Deletion
Location: chr8:41725843 (GRCh38)
Gene constraint: LOEUF 0.299 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.64 · 21 PDB
Residue 177: an α-helix; the '89 kda domain' region

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

Disease context

ANK1-related disorder

Similar variants

ANK1 p.Ala1768fs Likely pathogenic ★ same condition
ANK1 p.Asn568fs Likely pathogenic ★ same condition
ANK1 p.Gly592fs Pathogenic ★ same condition
ANK1 p.His1142fs Pathogenic ★ same condition
ANK1 p.His739fs Likely pathogenic ★ same condition
ANK1 p.Ile164fs Likely pathogenic ★ same condition
ANK1 p.Lys1826fs Likely pathogenic ★ same condition
ANK1 p.Tyr1514fs 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-leu177fs (accessed [today's date]).

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