Is ANK3 p.Ser32fs (c.93del) pathogenic?

ANK3 p.Ser32fs (c.93del) is classified Pathogenic in ANK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-10). Very rare (popmax 0.00223%, eas).

How common is ANK3 p.Ser32fs (c.93del) in the general population?

ANK3 p.Ser32fs (c.93del) is very rare (popmax 0.00223%, eas) (gnomAD).

ANK3 p.Ser32fs

c.93del · rs759973241 · VCV1455955

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 1 of 44
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,884 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00031% 5/1,613,666 alleles · very rare exomes 4/1,461,736 · genomes 1/151,930 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,884
Remaining individualsnot grpmax-eligible	0.0016%	62,472
European (non-Finnish)	0.000254%	393,306

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.Ser32fs
Coding: c.93del
MANE Select: NM_020987
dbSNP: rs759973241
Type: Deletion
Location: chr10:60389446 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)
Residue 32: the 'disordered' region

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

Similar variants

ANK3 p.Arg1456fs Pathogenic/Likely pathogenic ★★ same type
ANK3 p.Glu4256_Ile4257delinsVal Uncertain significance ★★ same type
ANK3 c.2614+6del Benign/Likely benign ★★ same type
ANK3 c.4351-10del Benign ★★ same type
ANK3 c.212_216+1del Likely pathogenic ★ same type
ANK3 p.Ala1197fs Pathogenic ★ same type
ANK3 p.Ala622fs Likely pathogenic ★ same type
ANK3 p.Asp1271fs Likely pathogenic ★ 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-ser32fs (accessed [today's date]).

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