Is ANK1 p.Ser1162= (c.3486C>T) pathogenic?

ANK1 p.Ser1162= (c.3486C>T) is classified Benign in ANK1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-01). Common (popmax 12.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with hereditary spherocytosis type 1.

What condition is associated with ANK1 p.Ser1162= (c.3486C>T)?

ANK1 p.Ser1162= (c.3486C>T) is associated with hereditary spherocytosis type 1 (ClinVar).

How is Hereditary spherocytosis inherited?

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

ANK1 p.Ser1162=

Q: How common is ANK1 p.Ser1162= (c.3486C>T) in the general population?

ANK1 p.Ser1162= (c.3486C>T) is common (popmax 12.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3486C>T · rs35964634 · VCV261306

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 12.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

hereditary spherocytosis type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.067	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.6	GERP -4
Overall
CADD	5.231	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 12.9% African / African-American · 9,671/75,008 alleles

Filtering AF 12.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 12.6%

Overall 0.834% 13,451/1,613,590 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	12.9%	8
Ashkenazi Jewishnot grpmax-eligible	2.07%	48
Middle Eastern	1.61%	62
Remaining individualsnot grpmax-eligible	1.2%	83
Admixed American	1.06%	94
South Asian	0.948%	105
European (non-Finnish)	0.0692%	1,446
East Asian	0.00891%	11,218
Finnishnot grpmax-eligible	0.00156%	63,924

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.Ser1162=
Coding: c.3486C>T
MANE Select: NM_000037
dbSNP: rs35964634
Type: single nucleotide variant
Location: chr8:41693944 (GRCh38)
Gene constraint: LOEUF 0.299 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.64 · 21 PDB
Residue 1162: the zu5 2 domain

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.Ser1162Gly 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-ser1162 (accessed [today's date]).

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