Is ANK1 p.Ala1840= (c.5520C>T) pathogenic?

ANK1 p.Ala1840= (c.5520C>T) is classified Conflicting classifications of pathogenicity in ANK1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-01-02). Rare (popmax 0.232%, eas); Associated with hereditary spherocytosis type 1.

What condition is associated with ANK1 p.Ala1840= (c.5520C>T)?

ANK1 p.Ala1840= (c.5520C>T) is associated with hereditary spherocytosis type 1 (ClinVar).

How common is ANK1 p.Ala1840= (c.5520C>T) in the general population?

ANK1 p.Ala1840= (c.5520C>T) is rare (popmax 0.232%, eas) (gnomAD).

How is Hereditary spherocytosis inherited?

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

ANK1 p.Ala1840=

c.5520C>T · rs116148295 · VCV911830

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.232%, eas)

Conditions

hereditary spherocytosis type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.9	GERP -4.2
Overall
CADD	2.844	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.232% East Asian · 104/44,872 alleles

Filtering AF 0.196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.182%

Overall 0.0083% 134/1,614,072 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.232%	431
Middle Eastern	0.0495%	2,021
South Asian	0.00769%	13,010
Remaining individualsnot grpmax-eligible	0.0064%	15,626
Admixed American	0.005%	20,006
African / African-American	0.004%	25,017
European (non-Finnish)	0.000847%	118,000

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ANK1
Protein: p.Ala1840=
Coding: c.5520C>T
MANE Select: NM_000037
dbSNP: rs116148295
Type: single nucleotide variant
Location: chr8:41661900 (GRCh38)
Gene constraint: LOEUF 0.299 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.64 · 21 PDB
Residue 1840: 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.Ala1840Thr Uncertain significance ★ ⚠ same residue
ANK1 c.1305+1G>A Pathogenic ★★ same condition
ANK1 c.1405-9G>A Pathogenic/Likely pathogenic ★★ same condition
ANK1 c.1702-2A>G Pathogenic/Likely pathogenic ★★ same condition
ANK1 c.1801-17G>A Pathogenic/Likely pathogenic ★★ same condition
ANK1 c.2296-1G>A Likely pathogenic ★★ same condition
ANK1 c.2296-2A>G Pathogenic/Likely pathogenic ★★ same condition
ANK1 c.2389-2A>G 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-ala1840 (accessed [today's date]).

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