Is ANK3 p.His422= (c.1266C>T) pathogenic?

ANK3 p.His422= (c.1266C>T) is classified Benign in ANK3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-29). Common (popmax 7.63%, eas) — too common for a highly-penetrant pathogenic allele.

ANK3 p.His422=

Q: How common is ANK3 p.His422= (c.1266C>T) in the general population?

ANK3 p.His422= (c.1266C>T) is common (popmax 7.63%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1266C>T · rs2297978 · VCV712382

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 7.63%, eas) — too common for a highly-penetrant pathogenic allele

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 -3.9	GERP -3.9
Overall
CADD	5.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.63% East Asian · 3,423/44,868 alleles

Filtering AF 7.42% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.33%

Overall 0.318% 5,124/1,613,670 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	7.63%	13
South Asian	1.01%	99
Remaining individualsnot grpmax-eligible	0.555%	180
African / African-American	0.163%	615
Finnishnot grpmax-eligible	0.151%	660
Ashkenazi Jewishnot grpmax-eligible	0.0405%	2,467
Admixed American	0.0167%	6,001
Middle Eastern	0.0165%	6,062
European (non-Finnish)	0.016%	6,241

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: ANK3
Protein: p.His422=
Coding: c.1266C>T
MANE Select: NM_020987
dbSNP: rs2297978
Type: single nucleotide variant
Location: chr10:60205819 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)

Full ANK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANK3 c.2382+6C>T Uncertain significance ★★ same type
ANK3 p.Ala1461Thr Uncertain significance ★★ ⚠ same type
ANK3 p.Ala1534Val Uncertain significance ★★ same type
ANK3 p.Ala1630Val Uncertain significance ★★ ⚠ same type
ANK3 p.Ala169Thr Uncertain significance ★★ same type
ANK3 p.Ala2023Thr Uncertain significance ★★ ⚠ same type
ANK3 p.Ala218Thr Uncertain significance ★★ same type
ANK3 p.Ala2223Thr Uncertain significance ★★ ⚠ same type

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/ank3-p-his422 (accessed [today's date]).

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