Is ATP10D p.Arg421Gln (c.1262G>A) pathogenic?

ATP10D p.Arg421Gln (c.1262G>A) is classified Uncertain significance in ATP10D (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely benign (0.1654); Ultra-rare (popmax 0.012%, afr).

How common is ATP10D p.Arg421Gln (c.1262G>A) in the general population?

ATP10D p.Arg421Gln (c.1262G>A) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about ATP10D p.Arg421Gln (c.1262G>A)?

AlphaMissense predicts likely benign (score 0.1654) — an in-silico prediction, not a clinical call.

ATP10D p.Arg421Gln

c.1262G>A · VCV4172566

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1654 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1654	likely benign
REVEL	0.655	pathogenic-leaning
SaProt	LLR -9.03	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 79 kb · p 0.0069 · regional, not allelic
Overall
CADD	32.0	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 0.012% African / African-American · 9/74,954 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00467%

Overall 0.00124% 20/1,613,022 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,328
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,582
East Asian	0.00223%	44,836
European (non-Finnish)	0.000763%	131,060

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: ATP10D
Protein: p.Arg421Gln
Coding: c.1262G>A
MANE Select: NM_020453
Type: single nucleotide variant
Location: chr4:47536804 (GRCh38)
Gene constraint: LOEUF 0.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.97

Full ATP10D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATP10D p.Arg182His Benign ★★ ⚠ same type
ATP10D p.Ala1236Thr Uncertain significance ★ ⚠ same type
ATP10D p.Ala35Thr Uncertain significance ★ ⚠ same type
ATP10D p.Ala35Val Uncertain significance ★ ⚠ same type
ATP10D p.Ala498Ser Uncertain significance ★ ⚠ same type
ATP10D p.Ala702Thr Uncertain significance ★ ⚠ same type
ATP10D p.Ala709Thr Uncertain significance ★ ⚠ same type
ATP10D p.Ala757Pro 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/atp10d-p-arg421gln (accessed [today's date]).

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