Is ANK3 p.Ile3117Val (c.9349A>G) pathogenic?

ANK3 p.Ile3117Val (c.9349A>G) is classified Benign in ANK3 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0902); Common (popmax 11%, nfe) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about ANK3 p.Ile3117Val (c.9349A>G)?

AlphaMissense predicts likely benign (score 0.0902) — an in-silico prediction, not a clinical call.

ANK3 p.Ile3117Val

Q: How common is ANK3 p.Ile3117Val (c.9349A>G) in the general population?

ANK3 p.Ile3117Val (c.9349A>G) is common (popmax 11%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.9349A>G · rs28932171 · VCV128384

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0902 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 11%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0902	likely benign
REVEL	0.09	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 5.3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 4,360 bp · p 0.0017 · regional, not allelic
Overall
CADD	19.15	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 11% European (non-Finnish) · 129,145/1,177,622 alleles

Filtering AF 10.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.9%

Overall 9.25% 148,984/1,611,226 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	11%	9
Remaining individualsnot grpmax-eligible	8.57%	12
Finnishnot grpmax-eligible	8.44%	12
Middle Eastern	7.86%	13
Amishnot grpmax-eligible	7.79%	13
Ashkenazi Jewishnot grpmax-eligible	6.22%	16
Admixed American	5.75%	17
South Asian	2.12%	47
African / African-American	1.77%	56
East Asian	0.0178%	5,609

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.Ile3117Val
Coding: c.9349A>G
MANE Select: NM_020987
dbSNP: rs28932171
Type: single nucleotide variant
Location: chr10:60071532 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)
Residue 3117: a UniProt-annotated variant site (in)

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

Similar variants

ANK3 p.Ile3117fs Pathogenic ★ same residue
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

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-ile3117val (accessed [today's date]).

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