Is ANK3 p.Asp874Glu (c.2622T>A) pathogenic?

ANK3 p.Asp874Glu (c.2622T>A) is classified Benign in ANK3 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-12-08). AlphaMissense: likely pathogenic (0.6317); Low-frequency (popmax 2.05%, sas).

How common is ANK3 p.Asp874Glu (c.2622T>A) in the general population?

ANK3 p.Asp874Glu (c.2622T>A) is low-frequency (popmax 2.05%, sas) (gnomAD).

What do computational predictors say about ANK3 p.Asp874Glu (c.2622T>A)?

AlphaMissense predicts likely pathogenic (score 0.6317) — an in-silico prediction, not a clinical call.

ANK3 p.Asp874Glu

c.2622T>A · rs564078262 · VCV1566252

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6317 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.05%, sas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.6317	likely pathogenic
REVEL	0.184	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.25	GERP -2.2, phastCons 0.26
Regional constraint	o/e 0.75	unconstrained · MANE · 105 kb · p 5.9e-15 · regional, not allelic
Overall
CADD	18.32	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.05% South Asian · 1,864/91,006 alleles

Filtering AF 1.97% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.94%

Overall 0.121% 1,949/1,613,494 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	2.05%	49
Remaining individualsnot grpmax-eligible	0.115%	868
Middle Eastern	0.0496%	2,016
East Asian	0.00223%	44,860
African / African-American	0.00133%	74,956
European (non-Finnish)	0.000678%	147,464

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.Asp874Glu
Coding: c.2622T>A
MANE Select: NM_020987
dbSNP: rs564078262
Type: single nucleotide variant
Location: chr10:60139080 (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-asp874glu (accessed [today's date]).

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