Is ANK1 p.Ala1867Val (c.5600C>T) pathogenic?

ANK1 p.Ala1867Val (c.5600C>T) is classified Conflicting classifications of pathogenicity in ANK1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-10-27). Ultra-rare (popmax 0.0493%, mid); Associated with hereditary spherocytosis type 1.

What condition is associated with ANK1 p.Ala1867Val (c.5600C>T)?

ANK1 p.Ala1867Val (c.5600C>T) is associated with hereditary spherocytosis type 1 (ClinVar).

How common is ANK1 p.Ala1867Val (c.5600C>T) in the general population?

ANK1 p.Ala1867Val (c.5600C>T) is ultra-rare (popmax 0.0493%, mid) (gnomAD).

How is Hereditary spherocytosis inherited?

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

ANK1 p.Ala1867Val

c.5600C>T · rs767580738 · VCV1330617

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0493%, mid)

Conditions

hereditary spherocytosis type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.343	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 23 kb · p 0.11 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0493% Middle Eastern · 3/6,084 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00715%

Overall 0.00229% 37/1,613,846 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0493%	2,028
East Asian	0.0178%	5,611
Admixed American	0.00667%	15,000
African / African-American	0.00401%	24,962
South Asian	0.00329%	30,359
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.00127%	78,668

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.Ala1867Val
Coding: c.5600C>T
MANE Select: NM_000037
dbSNP: rs767580738
Type: single nucleotide variant
Location: chr8:41661509 (GRCh38)
Gene constraint: LOEUF 0.299 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.64 · 21 PDB
Residue 1867: the '55 kda regulatory 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.Ala1867= Conflicting classifications of pathogenicity ★ 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-ala1867val (accessed [today's date]).

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