Is ANK1 p.Thr790= (c.2370G>T) pathogenic?

ANK1 p.Thr790= (c.2370G>T) is classified Conflicting classifications of pathogenicity in ANK1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-01). Rare (popmax 0.369%, sas); Associated with hereditary spherocytosis type 1.

What condition is associated with ANK1 p.Thr790= (c.2370G>T)?

ANK1 p.Thr790= (c.2370G>T) is associated with hereditary spherocytosis type 1 (ClinVar).

How common is ANK1 p.Thr790= (c.2370G>T) in the general population?

ANK1 p.Thr790= (c.2370G>T) is rare (popmax 0.369%, sas) (gnomAD).

How is Hereditary spherocytosis inherited?

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

ANK1 p.Thr790=

c.2370G>T · rs540304535 · VCV363016

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.369%, sas)

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 -20	GERP -4.3
Overall
CADD	0.344	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.369% South Asian · 336/91,080 alleles

Filtering AF 0.336% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.324%

Overall 0.0216% 349/1,614,148 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.369%	271
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.0128%	7,813

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.Thr790=
Coding: c.2370G>T
MANE Select: NM_000037
dbSNP: rs540304535
Type: single nucleotide variant
Location: chr8:41702070 (GRCh38)
Gene constraint: LOEUF 0.299 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.64 · 21 PDB
Residue 790: the '89 kda domain' 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.Thr790Met 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-thr790 (accessed [today's date]).

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