Is ANKS3 p.Pro601Ser (c.1801C>T) pathogenic?

ANKS3 p.Pro601Ser (c.1801C>T) is classified Uncertain significance in ANKS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely benign (0.0683); Very rare (popmax 8.54e-05%, nfe).

How common is ANKS3 p.Pro601Ser (c.1801C>T) in the general population?

ANKS3 p.Pro601Ser (c.1801C>T) is very rare (popmax 8.54e-05%, nfe) (gnomAD).

What do computational predictors say about ANKS3 p.Pro601Ser (c.1801C>T)?

AlphaMissense predicts likely benign (score 0.0683) — an in-silico prediction, not a clinical call.

ANKS3 p.Pro601Ser

c.1801C>T · rs769008777 · VCV2249733

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0683 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.54e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0683	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -6.60	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 4.7	GERP -2.4, phastCons 1
Regional constraint	o/e 1.30	unconstrained · MANE · 33 kb · p 3.2e-19 · regional, not allelic
Overall
CADD	4.67	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 8.54e-05% European (non-Finnish) · 1/1,171,632 alleles

Overall 6.93e-05% 1/1,442,254 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: ANKS3
Protein: p.Pro601Ser
Coding: c.1801C>T
MANE Select: NM_133450
dbSNP: rs769008777
Type: single nucleotide variant
Location: chr16:4697986 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.94 · 2 PDB

Full ANKS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANKS3 p.Cys168Gly Likely benign ★★ same type
ANKS3 p.Glu328= Benign ★★ same type
ANKS3 p.Gly25Glu Benign ★★ same type
ANKS3 p.His377= Benign ★★ same type
ANKS3 p.Leu14= Benign/Likely benign ★★ same type
ANKS3 p.Val585= Benign ★★ same type
ANKS3 p.Ala118Thr Uncertain significance ★ same type
ANKS3 p.Ala271Thr 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/anks3-p-pro601ser (accessed [today's date]).

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