Is ANKS1A p.Ala523Pro (c.1567G>C) pathogenic?

ANKS1A p.Ala523Pro (c.1567G>C) is classified Likely benign in ANKS1A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-19). AlphaMissense: likely benign (0.0707); Ultra-rare (popmax 0.0329%, mid).

How common is ANKS1A p.Ala523Pro (c.1567G>C) in the general population?

ANKS1A p.Ala523Pro (c.1567G>C) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about ANKS1A p.Ala523Pro (c.1567G>C)?

AlphaMissense predicts likely benign (score 0.0707) — an in-silico prediction, not a clinical call.

ANKS1A p.Ala523Pro

c.1567G>C · rs755087986 · VCV2223395

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0707 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0707	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -5.88	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.11	GERP -3.9
Regional constraint	o/e 0.80	unconstrained · MANE · 105 kb · p 1.7e-11 · regional, not allelic
Overall
CADD	0.375	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 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00638% 103/1,613,668 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Admixed American	0.0267%	3,749
Remaining individualsnot grpmax-eligible	0.00961%	10,408
European (non-Finnish)	0.0067%	14,935

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.Ala523Pro
Coding: c.1567G>C
MANE Select: NM_015245
dbSNP: rs755087986
Type: single nucleotide variant
Location: chr6:35017616 (GRCh38)
Gene constraint: LOEUF 0.549 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.78 · 3 PDB

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

Similar variants

ANKS1A p.Ala523Thr Likely benign ★ same residue
ANKS1A p.Pro1089= Likely benign ★★ same type
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

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-ala523pro (accessed [today's date]).

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