Is ATPAF2 p.Arg263Gln (c.788G>A) pathogenic?

ATPAF2 p.Arg263Gln (c.788G>A) is classified Uncertain significance in ATPAF2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-03). AlphaMissense: likely benign (0.1235); Ultra-rare (popmax 0.033%, mid).

How common is ATPAF2 p.Arg263Gln (c.788G>A) in the general population?

ATPAF2 p.Arg263Gln (c.788G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about ATPAF2 p.Arg263Gln (c.788G>A)?

AlphaMissense predicts likely benign (score 0.1235) — an in-silico prediction, not a clinical call.

ATPAF2 p.Arg263Gln

c.788G>A · VCV3602240

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1235 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1235	likely benign
REVEL	0.411	indeterminate
SaProt	LLR -10.26	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.84	GERP 1.6, phastCons 0.26
Regional constraint	o/e 0.90	unconstrained · MANE · 7,840 bp · p 0.15 · regional, not allelic
Overall
CADD	21.7	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 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.0013% 19/1,461,752 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0064%	15,625
Admixed American	0.00333%	30,017
European (non-Finnish)	0.000932%	107,275

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: ATPAF2
Protein: p.Arg263Gln
Coding: c.788G>A
MANE Select: NM_145691
Type: single nucleotide variant
Location: chr17:18018631 (GRCh38)
Gene constraint: LOEUF 1.1 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.07

Full ATPAF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATPAF2 p.Arg263Trp Uncertain significance ★ ⚠ same residue
ATPAF2 c.-90C>A Uncertain significance ★★ same type
ATPAF2 c.*132C>T Uncertain significance ★★ same type
ATPAF2 p.Ala130Glu Uncertain significance ★★ ⚠ same type
ATPAF2 p.Ala267Thr Uncertain significance ★★ ⚠ same type
ATPAF2 p.Ala268Thr Uncertain significance ★★ ⚠ same type
ATPAF2 p.Arg14Gly Uncertain significance ★★ ⚠ same type
ATPAF2 p.Arg189Gln 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/atpaf2-p-arg263gln (accessed [today's date]).

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