Is ANK1 p.Thr401= (c.1203C>T) pathogenic?

ANK1 p.Thr401= (c.1203C>T) is classified Conflicting classifications of pathogenicity in ANK1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-11-21). Ultra-rare (popmax 0.0603%, nfe); Associated with Spherocytosis.

What condition is associated with ANK1 p.Thr401= (c.1203C>T)?

ANK1 p.Thr401= (c.1203C>T) is associated with Spherocytosis, hereditary spherocytosis type 1 (ClinVar).

How common is ANK1 p.Thr401= (c.1203C>T) in the general population?

ANK1 p.Thr401= (c.1203C>T) is ultra-rare (popmax 0.0603%, nfe) (gnomAD).

ANK1 p.Thr401=

c.1203C>T · rs145628190 · VCV363034

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0603%, 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 -20	GERP -4.3
Overall
CADD	0.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0603% European (non-Finnish) · 712/1,179,938 alleles

Filtering AF 0.0566% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0552%

Overall 0.0525% 847/1,613,610 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.199%	502
Remaining individualsnot grpmax-eligible	0.0784%	1,275
European (non-Finnish)grpmax	0.0603%	1,657
Middle Eastern	0.0329%	3,042
African / African-American	0.0134%	7,491
Finnishnot grpmax-eligible	0.0125%	7,969
Admixed American	0.00833%	11,999
East Asian	0.00223%	44,884
South Asian	0.0011%	91,062

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr401=
Coding: c.1203C>T
MANE Select: NM_000037
dbSNP: rs145628190
Type: single nucleotide variant
Location: chr8:41718109 (GRCh38)
Gene constraint: LOEUF 0.299 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.64 · 21 PDB
Residue 401: 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 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
ANK1 c.2462-2A>G 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-thr401 (accessed [today's date]).

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