Is ATP9B p.Thr117Pro (c.349A>C) pathogenic?

ATP9B p.Thr117Pro (c.349A>C) is classified Uncertain significance in ATP9B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely pathogenic (0.579); Very rare (popmax 0.00144%, nfe).

How common is ATP9B p.Thr117Pro (c.349A>C) in the general population?

ATP9B p.Thr117Pro (c.349A>C) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about ATP9B p.Thr117Pro (c.349A>C)?

AlphaMissense predicts likely pathogenic (score 0.579) — an in-silico prediction, not a clinical call.

ATP9B p.Thr117Pro

c.349A>C · rs751763607 · VCV2311463

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.579 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.579	likely pathogenic
REVEL	0.585	indeterminate
SaProt	LLR -15.18	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 2.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 308 kb · p 0.95 · regional, not allelic
Overall
CADD	25.1	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 0.00144% European (non-Finnish) · 17/1,178,408 alleles

Filtering AF 0.000879% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.00118% 19/1,611,294 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00321%	31,186
European (non-Finnish)grpmax	0.00144%	69,318

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr117Pro
Coding: c.349A>C
MANE Select: NM_198531
dbSNP: rs751763607
Type: single nucleotide variant
Location: chr18:79110410 (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.Thr117= Benign ★★ same residue
ATP9B p.Thr117Ile Uncertain significance ★ ⚠ same residue
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.Ala1044Val Uncertain significance ★ ⚠ same type
ATP9B p.Ala1049Thr 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-thr117pro (accessed [today's date]).

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