Is ATP9B p.Ser1007Thr (c.3019T>A) pathogenic?

ATP9B p.Ser1007Thr (c.3019T>A) is classified Uncertain significance in ATP9B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely benign (0.1176); Ultra-rare (popmax 0.0201%, eas).

How common is ATP9B p.Ser1007Thr (c.3019T>A) in the general population?

ATP9B p.Ser1007Thr (c.3019T>A) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

What do computational predictors say about ATP9B p.Ser1007Thr (c.3019T>A)?

AlphaMissense predicts likely benign (score 0.1176) — an in-silico prediction, not a clinical call.

ATP9B p.Ser1007Thr

c.3019T>A · VCV3974869

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1176 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1176	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -12.30	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -2.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 308 kb · p 0.95 · regional, not allelic
Overall
CADD	16.34	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 0.0201% East Asian · 9/44,874 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.000617% 9/1,457,648 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: ATP9B
Protein: p.Ser1007Thr
Coding: c.3019T>A
MANE Select: NM_198531
Type: single nucleotide variant
Location: chr18:79372831 (GRCh38)
Gene constraint: LOEUF 0.857 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.49

Full ATP9B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATP9B p.Thr353Ala Uncertain significance ★★ ⚠ same type
ATP9B p.Asp504Asn Benign ★★ same type
ATP9B p.Leu384= Benign ★★ same type
ATP9B p.Phe570= Benign ★★ same type
ATP9B p.Thr117= Benign ★★ same type
ATP9B p.Ala1044Val Uncertain significance ★ ⚠ same type
ATP9B p.Ala1049Thr Uncertain significance ★ ⚠ same type
ATP9B p.Ala1085Pro 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/atp9b-p-ser1007thr (accessed [today's date]).

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