Is ANKS1A p.Pro407Ser (c.1219C>T) pathogenic?

ANKS1A p.Pro407Ser (c.1219C>T) is classified Uncertain significance in ANKS1A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-29). AlphaMissense: likely benign (0.2863); Ultra-rare (popmax 0.0198%, sas).

How common is ANKS1A p.Pro407Ser (c.1219C>T) in the general population?

ANKS1A p.Pro407Ser (c.1219C>T) is ultra-rare (popmax 0.0198%, sas) (gnomAD).

What do computational predictors say about ANKS1A p.Pro407Ser (c.1219C>T)?

AlphaMissense predicts likely benign (score 0.2863) — an in-silico prediction, not a clinical call.

ANKS1A p.Pro407Ser

c.1219C>T · rs199740223 · VCV2399101

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2863 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0198%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2863	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -8.55	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 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 105 kb · p 1.7e-11 · regional, not allelic
Overall
CADD	22.2	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 0.0198% South Asian · 18/91,008 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00123% 18/1,461,574 alleles · ultra-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.Pro407Ser
Coding: c.1219C>T
MANE Select: NM_015245
dbSNP: rs199740223
Type: single nucleotide variant
Location: chr6:34989233 (GRCh38)
Gene constraint: LOEUF 0.549 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 60.78 · 3 PDB
Residue 407: the 'disordered' region

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-pro407ser (accessed [today's date]).

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