Is ANKS1A p.Gly2Arg (c.4G>A) pathogenic?

ANKS1A p.Gly2Arg (c.4G>A) is classified Uncertain significance in ANKS1A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-19). AlphaMissense: likely pathogenic (0.975); Very rare (popmax 0.000198%, nfe).

How common is ANKS1A p.Gly2Arg (c.4G>A) in the general population?

ANKS1A p.Gly2Arg (c.4G>A) is very rare (popmax 0.000198%, nfe) (gnomAD).

What do computational predictors say about ANKS1A p.Gly2Arg (c.4G>A)?

AlphaMissense predicts likely pathogenic (score 0.975) — an in-silico prediction, not a clinical call.

ANKS1A p.Gly2Arg

c.4G>A · rs2533790738 · VCV2336375

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.975 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000198%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.975	likely pathogenic
REVEL	0.414	indeterminate
SaProt	LLR -11.99	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 175 bp · p 0.31 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000198% European (non-Finnish) · 2/1,012,584 alleles

Filtering AF 3.3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2e-05%

Overall 0.000179% 2/1,120,230 alleles · very rare

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.Gly2Arg
Coding: c.4G>A
MANE Select: NM_015245
dbSNP: rs2533790738
Type: single nucleotide variant
Location: chr6:34889406 (GRCh38)
Gene constraint: LOEUF 0.549 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.78 · 3 PDB
Residue 2: a modified residue (n-acetylglycine)

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

Similar variants

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
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-gly2arg (accessed [today's date]).

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