Is ANK1 p.Ala1367= (c.4101C>T) pathogenic?

ANK1 p.Ala1367= (c.4101C>T) is classified Benign/Likely benign in ANK1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-03). Common (popmax 47.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Spherocytosis.

What condition is associated with ANK1 p.Ala1367= (c.4101C>T)?

ANK1 p.Ala1367= (c.4101C>T) is associated with Spherocytosis, hereditary spherocytosis type 1 (ClinVar).

ANK1 p.Ala1367=

Q: How common is ANK1 p.Ala1367= (c.4101C>T) in the general population?

ANK1 p.Ala1367= (c.4101C>T) is common (popmax 47.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.4101C>T · rs7816734 · VCV261309

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 47.8%, afr) — too common for a highly-penetrant pathogenic allele

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 5.7	GERP -4.3, phastCons 1
Overall
CADD	11.72	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 47.8% African / African-American · 35,846/74,952 alleles

Filtering AF 47.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 47.2%

Overall 7.59% 122,557/1,614,014 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	47.8%	2
Remaining individualsnot grpmax-eligible	8.19%	12
East Asian	7.35%	14
Amishnot grpmax-eligible	7.02%	14
Ashkenazi Jewishnot grpmax-eligible	6.72%	15
Middle Eastern	5.72%	17
European (non-Finnish)	5.64%	18
Admixed American	5.24%	19
South Asian	4.52%	22
Finnishnot grpmax-eligible	3.33%	30

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.Ala1367=
Coding: c.4101C>T
MANE Select: NM_000037
dbSNP: rs7816734
Type: single nucleotide variant
Location: chr8:41690230 (GRCh38)
Gene constraint: LOEUF 0.299 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.64 · 21 PDB

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.Ala1367Thr Likely benign ★★ same residue
ANK1 p.Ala1367fs Likely pathogenic ★ 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

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-ala1367 (accessed [today's date]).

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