Is ATP6AP1 p.Arg330Cys (c.988C>T) pathogenic?

ATP6AP1 p.Arg330Cys (c.988C>T) is classified Uncertain significance in ATP6AP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-14). AlphaMissense: likely benign (0.1719); Very rare (popmax 0.00874%, afr); Associated with Inborn genetic diseases.

What condition is associated with ATP6AP1 p.Arg330Cys (c.988C>T)?

ATP6AP1 p.Arg330Cys (c.988C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ATP6AP1 p.Arg330Cys (c.988C>T) in the general population?

ATP6AP1 p.Arg330Cys (c.988C>T) is very rare (popmax 0.00874%, afr) (gnomAD).

What do computational predictors say about ATP6AP1 p.Arg330Cys (c.988C>T)?

AlphaMissense predicts likely benign (score 0.1719) — an in-silico prediction, not a clinical call.

ATP6AP1 p.Arg330Cys

c.988C>T · VCV3714196

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1719 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00874%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1719	likely benign
REVEL	0.334	indeterminate
SaProt	LLR -11.41	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP 0.38, phastCons 0.91
Regional constraint	o/e 0.61	unconstrained · MANE · 3,476 bp · p 5.5e-10 · regional, not allelic
Overall
CADD	25.7	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 0.00874% African / African-American · 5/57,227 alleles

Filtering AF 0.00338% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00215%

Overall 0.00174% 21/1,210,111 alleles · very rare exomes 19/1,098,021 · genomes 2/112,090 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00874%	11,445
Admixed American	0.00218%	45,858
Remaining individualsnot grpmax-eligible	0.0021%	47,586
European (non-Finnish)	0.00156%	63,937

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: ATP6AP1
Protein: p.Arg330Cys
Coding: c.988C>T
MANE Select: NM_001183
Type: single nucleotide variant
Location: chrX:154435290 (GRCh38)
Structure: AlphaFold pLDDT 79.60 · 9 PDB
Residue 330: a β-strand

Full ATP6AP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ATP6AP1 p.Arg330His Benign ★ same residue
ATP6AP1 c.557+6G>A Uncertain significance ★★ same condition
ATP6AP1 p.Arg344His Uncertain significance ★★ ⚠ same condition
ATP6AP1 p.His158Arg Uncertain significance ★★ ⚠ same condition
ATP6AP1 p.Lys247Gln Uncertain significance ★★ ⚠ same condition
ATP6AP1 p.Pro174Arg Uncertain significance ★★ same condition
ATP6AP1 p.Val141Leu Uncertain significance ★★ ⚠ same condition
ATP6AP1 p.Val353Ile Uncertain significance ★★ ⚠ same condition

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/atp6ap1-p-arg330cys (accessed [today's date]).

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