Is ANK3 p.Ala5Ser (c.13G>T) pathogenic?

ANK3 p.Ala5Ser (c.13G>T) is classified Uncertain significance in ANK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-29). Very rare (popmax 0.00252%, nfe); Associated with ANK3-related neurodevelopmental disorder.

What condition is associated with ANK3 p.Ala5Ser (c.13G>T)?

ANK3 p.Ala5Ser (c.13G>T) is associated with ANK3-related neurodevelopmental disorder (ClinVar).

How common is ANK3 p.Ala5Ser (c.13G>T) in the general population?

ANK3 p.Ala5Ser (c.13G>T) is very rare (popmax 0.00252%, nfe) (gnomAD).

ANK3 p.Ala5Ser

c.13G>T · rs777570818 · VCV1696536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00252%, nfe)

Conditions

ANK3-related neurodevelopmental disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.071	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -1.8
Overall
CADD	3.089	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00252% European (non-Finnish) · 25/991,068 alleles

Filtering AF 0.00173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00146%

Overall 0.0021% 26/1,235,916 alleles · very rare exomes 22/1,083,940 · genomes 4/151,976 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00252%	39,643
African / African-American	0.00155%	64,346

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.Ala5Ser
Coding: c.13G>T
MANE Select: NM_020987 · reported on NM_001204403
dbSNP: rs777570818
Type: single nucleotide variant
Location: chr10:60733307 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)
Residue 5: the 'disordered' region

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

Disease context

ANK3-related neurodevelopmental disorder

Similar variants

ANK3 p.Arg1243His Uncertain significance ★★ ⚠ same condition
ANK3 p.Gly1194Glu Uncertain significance ★★ ⚠ same condition
ANK3 p.Arg4225Ter Uncertain significance ★ same condition
ANK3 p.Asp553Asn Uncertain significance ★ ⚠ same condition
ANK3 p.His3880Tyr Uncertain significance ★ ⚠ same condition
ANK3 p.Lys4020Asn Uncertain significance ★ ⚠ same condition
ANK3 p.Asp2977Asn Uncertain significance ⚠ same condition
ANK3 p.Met3731Val Uncertain significance ⚠ 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/ank3-p-ala5ser (accessed [today's date]).

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