Is ANK1 p.Ala530= (c.1590C>T) pathogenic?

ANK1 p.Ala530= (c.1590C>T) is classified Conflicting classifications of pathogenicity in ANK1 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-28). Low-frequency (popmax 1.38%, nfe); Associated with Spherocytosis.

What condition is associated with ANK1 p.Ala530= (c.1590C>T)?

ANK1 p.Ala530= (c.1590C>T) is associated with Spherocytosis, hereditary spherocytosis type 1 (ClinVar).

How common is ANK1 p.Ala530= (c.1590C>T) in the general population?

ANK1 p.Ala530= (c.1590C>T) is low-frequency (popmax 1.38%, nfe) (gnomAD).

ANK1 p.Ala530=

c.1590C>T · rs61758865 · VCV261292

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.38%, nfe)

Conditions

Spherocytosis

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 -2.5	GERP -4
Overall
CADD	7.649	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.38% European (non-Finnish) · 16,253/1,179,970 alleles

Filtering AF 1.36% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.35%

Overall 1.07% 17,239/1,613,460 alleles · low-frequency

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.38%	73
Remaining individualsnot grpmax-eligible	0.719%	139
Admixed American	0.245%	408
Amishnot grpmax-eligible	0.219%	456
Ashkenazi Jewishnot grpmax-eligible	0.216%	463
African / African-American	0.211%	475
Finnishnot grpmax-eligible	0.159%	627
Middle Eastern	0.143%	697
South Asian	0.0615%	1,626

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.Ala530=
Coding: c.1590C>T
MANE Select: NM_000037
dbSNP: rs61758865
Type: single nucleotide variant
Location: chr8:41715664 (GRCh38)
Gene constraint: LOEUF 0.299 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.64 · 21 PDB
Residue 530: the '89 kda domain' region

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

Disease context

Spherocytosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary spherocytosis type 1

Similar variants

ANK1 p.Ala530Thr 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-ala530 (accessed [today's date]).

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