Is ANK1 p.Pro737= (c.2211C>G) pathogenic?

ANK1 p.Pro737= (c.2211C>G) is classified Benign/Likely benign in ANK1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-16). Low-frequency (popmax 3.82%, afr); Associated with hereditary spherocytosis type 1.

What condition is associated with ANK1 p.Pro737= (c.2211C>G)?

ANK1 p.Pro737= (c.2211C>G) is associated with hereditary spherocytosis type 1 (ClinVar).

How common is ANK1 p.Pro737= (c.2211C>G) in the general population?

ANK1 p.Pro737= (c.2211C>G) 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.Pro737=

c.2211C>G · rs34194642 · VCV363017

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 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	0.148	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.58	GERP -4.3, phastCons 0.99
Overall
CADD	2.359	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.82% African / African-American · 2,863/75,040 alleles

Filtering AF 3.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.65%

Overall 0.292% 4,714/1,614,076 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.82%	26
East Asian	3.06%	33
Remaining individualsnot grpmax-eligible	0.378%	265
Admixed American	0.242%	414
South Asian	0.0538%	1,859
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.0039%	25,653

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.Pro737=
Coding: c.2211C>G
MANE Select: NM_000037
dbSNP: rs34194642
Type: single nucleotide variant
Location: chr8:41704125 (GRCh38)
Gene constraint: LOEUF 0.299 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.64 · 21 PDB
Residue 737: an α-helix; 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 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-pro737 (accessed [today's date]).

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