Is ATP9B p.Arg20Ser (c.58C>A) pathogenic?

ATP9B p.Arg20Ser (c.58C>A) is classified Uncertain significance in ATP9B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely benign (0.2287); Rare (popmax 0.209%, afr).

How common is ATP9B p.Arg20Ser (c.58C>A) in the general population?

ATP9B p.Arg20Ser (c.58C>A) is rare (popmax 0.209%, afr) (gnomAD).

What do computational predictors say about ATP9B p.Arg20Ser (c.58C>A)?

AlphaMissense predicts likely benign (score 0.2287) — an in-silico prediction, not a clinical call.

ATP9B p.Arg20Ser

c.58C>A · VCV4181102

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2287 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.209%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2287	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	LLR -6.27	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 1.8	GERP 0.63, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 308 kb · p 0.95 · regional, not allelic
Overall
CADD	17.67	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 0.209% African / African-American · 145/69,474 alleles

Filtering AF 0.181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.171%

Overall 0.011% 166/1,504,180 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.209%	479
Remaining individualsnot grpmax-eligible	0.0156%	6,405
Admixed American	0.0136%	7,328
European (non-Finnish)	0.000531%	188,203

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.Arg20Ser
Coding: c.58C>A
MANE Select: NM_198531
Type: single nucleotide variant
Location: chr18:79069468 (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.Arg20Gly 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.Thr117= 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-arg20ser (accessed [today's date]).

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