Is ANKS1A p.Ser66= (c.198C>T) pathogenic?

ANKS1A p.Ser66= (c.198C>T) is classified Likely benign in ANKS1A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-16). Very rare (popmax 0.00892%, eas).

How common is ANKS1A p.Ser66= (c.198C>T) in the general population?

ANKS1A p.Ser66= (c.198C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

ANKS1A p.Ser66=

c.198C>T · rs774910506 · VCV2603876

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

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 4	GERP 2.3, phastCons 1
Overall
CADD	18.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,864 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00031% 5/1,612,270 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00892%	11,216
European (non-Finnish)	8.48e-05%	1,179,491

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.Ser66=
Coding: c.198C>T
MANE Select: NM_015245
dbSNP: rs774910506
Type: single nucleotide variant
Location: chr6:34967239 (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.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-ser66 (accessed [today's date]).

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