Is ANKS1A p.Pro1089= (c.3267G>A) pathogenic?

ANKS1A p.Pro1089= (c.3267G>A) is classified Likely benign in ANKS1A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-20). Ultra-rare (popmax 0.0317%, amr).

How common is ANKS1A p.Pro1089= (c.3267G>A) in the general population?

ANKS1A p.Pro1089= (c.3267G>A) is ultra-rare (popmax 0.0317%, amr) (gnomAD).

ANKS1A p.Pro1089=

c.3267G>A · rs202217863 · VCV2656506

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0317%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.9	GERP -4.9
Overall
CADD	8.555	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0317% Admixed American · 19/59,874 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.0145% 234/1,612,756 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0474%	2,111
Admixed Americangrpmax	0.0317%	3,151
Remaining individualsnot grpmax-eligible	0.0176%	5,677
European (non-Finnish)	0.0157%	6,376
East Asian	0.00446%	22,427
Finnishnot grpmax-eligible	0.00157%	63,516
African / African-American	0.00133%	74,988
South Asian	0.0011%	90,962

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ANKS1A
Protein: p.Pro1089=
Coding: c.3267G>A
MANE Select: NM_015245
dbSNP: rs202217863
Type: single nucleotide variant
Location: chr6:35085900 (GRCh38)
Gene constraint: LOEUF 0.549 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.78 · 3 PDB
Residue 1089: the pid domain; the 'disordered' region

Full ANKS1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKS1A p.Pro1089Arg Uncertain significance ★ ⚠ same residue
ANKS1A p.Ala1061Val Uncertain significance ★ ⚠ same type
ANKS1A p.Ala1076Thr Uncertain significance ★ ⚠ same type
ANKS1A p.Ala1101Thr Uncertain significance ★ ⚠ same type
ANKS1A p.Ala268Thr Uncertain significance ★ ⚠ same type
ANKS1A p.Ala488Val Uncertain significance ★ ⚠ same type
ANKS1A p.Ala554Asp Uncertain significance ★ ⚠ same type
ANKS1A p.Ala603Val 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/anks1a-p-pro1089 (accessed [today's date]).

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