Is ANK3 p.Arg915Cys (c.2743C>T) pathogenic?

ANK3 p.Arg915Cys (c.2743C>T) is classified Uncertain significance in ANK3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-01-01). AlphaMissense: likely pathogenic (0.7625); Very rare (popmax 0.00447%, eas).

How common is ANK3 p.Arg915Cys (c.2743C>T) in the general population?

ANK3 p.Arg915Cys (c.2743C>T) is very rare (popmax 0.00447%, eas) (gnomAD).

What do computational predictors say about ANK3 p.Arg915Cys (c.2743C>T)?

AlphaMissense predicts likely pathogenic (score 0.7625) — an in-silico prediction, not a clinical call.

ANK3 p.Arg915Cys

c.2743C>T · rs762868986 · VCV2055881

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7625 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00447%, eas)

Computational evidence

Protein change
AlphaMissense	0.7625	likely pathogenic
REVEL	0.489	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.64 · evaluated, not missing
Pangolin	Δ0.22	gain · loss 0.14 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 12	GERP 6.5, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 105 kb · p 5.9e-15 · regional, not allelic
Overall
CADD	33.0	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 0.00447% East Asian · 2/44,786 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00143% 23/1,612,284 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00447%	22,393
Admixed American	0.00335%	29,855
European (non-Finnish)	0.00144%	69,374
African / African-American	0.00134%	74,858
South Asian	0.0011%	90,692

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.Arg915Cys
Coding: c.2743C>T
MANE Select: NM_020987
dbSNP: rs762868986
Type: single nucleotide variant
Location: chr10:60134369 (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 p.Arg915His Conflicting classifications of pathogenicity ★ same residue
ANK3 p.Arg915= Likely benign ★ 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

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-arg915cys (accessed [today's date]).

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