Is ANK1 p.Ala151Asp (c.452C>A) pathogenic?

ANK1 p.Ala151Asp (c.452C>A) is classified Uncertain significance in ANK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-29). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1; Associated with ANK1-related disorder.

What condition is associated with ANK1 p.Ala151Asp (c.452C>A)?

ANK1 p.Ala151Asp (c.452C>A) is associated with ANK1-related disorder (ClinVar).

How common is ANK1 p.Ala151Asp (c.452C>A) in the general population?

ANK1 p.Ala151Asp (c.452C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANK1 p.Ala151Asp (c.452C>A)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

ANK1 p.Ala151Asp

c.452C>A · rs2486988372 · VCV2637207

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ANK1-related disorder

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic · top 1% in ANK1
REVEL	0.812	moderately pathogenic-leaning
SaProt	LLR -17.13	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.28	constrained · MANE · 1,393 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	27.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANK1
Protein: p.Ala151Asp
Coding: c.452C>A
MANE Select: NM_000037
dbSNP: rs2486988372
Type: single nucleotide variant
Location: chr8:41725921 (GRCh38)
Gene constraint: LOEUF 0.299 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.64 · 21 PDB
Residue 151: 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 c.1801-17G>A Pathogenic/Likely pathogenic ★★ same condition
ANK1 p.Arg1053Ter Pathogenic ★★ same condition
ANK1 p.Arg1682Ter Pathogenic ★★ same condition
ANK1 p.Arg281Ter Pathogenic/Likely pathogenic ★★ same condition
ANK1 p.Arg286Ter Pathogenic ★★ same condition
ANK1 p.Ser1646Ter Pathogenic/Likely pathogenic ★★ same condition
ANK1 p.Trp1600Ter Pathogenic/Likely pathogenic ★★ same condition
ANK1 p.Tyr1750Ter 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-ala151asp (accessed [today's date]).

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