Is ANK1 p.Ile990= (c.2970C>T) pathogenic?

ANK1 p.Ile990= (c.2970C>T) is classified Benign/Likely benign in ANK1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-28). Low-frequency (popmax 3.82%, afr); Associated with hereditary spherocytosis type 1.

What condition is associated with ANK1 p.Ile990= (c.2970C>T)?

ANK1 p.Ile990= (c.2970C>T) is associated with hereditary spherocytosis type 1 (ClinVar).

How common is ANK1 p.Ile990= (c.2970C>T) in the general population?

ANK1 p.Ile990= (c.2970C>T) is low-frequency (popmax 3.82%, afr) (gnomAD).

How is Hereditary spherocytosis inherited?

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

ANK1 p.Ile990=

c.2970C>T · rs34969689 · VCV783522

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.82%, afr)

Conditions

hereditary spherocytosis type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.082	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.9	GERP -4.3
Overall
CADD	0.591	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.82% African / African-American · 2,868/75,004 alleles

Filtering AF 3.71% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.66%

Overall 0.209% 3,371/1,613,940 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.82%	26
Admixed American	0.31%	323
Remaining individualsnot grpmax-eligible	0.269%	372
Middle Eastern	0.198%	505
South Asian	0.011%	9,107
European (non-Finnish)	0.0107%	9,365
East Asian	0.00223%	44,858

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.Ile990=
Coding: c.2970C>T
MANE Select: NM_000037
dbSNP: rs34969689
Type: single nucleotide variant
Location: chr8:41695322 (GRCh38)
Gene constraint: LOEUF 0.299 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.64 · 21 PDB
Residue 990: a β-strand; the zu5 1 domain

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.Ile990Asn 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-ile990 (accessed [today's date]).

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