Is ATAD2 p.Arg393Pro (c.1178G>C) pathogenic?

ATAD2 p.Arg393Pro (c.1178G>C) is classified Uncertain significance in ATAD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-12). AlphaMissense: ambiguous (0.518); Ultra-rare (popmax 0.0265%, sas).

How common is ATAD2 p.Arg393Pro (c.1178G>C) in the general population?

ATAD2 p.Arg393Pro (c.1178G>C) is ultra-rare (popmax 0.0265%, sas) (gnomAD).

What do computational predictors say about ATAD2 p.Arg393Pro (c.1178G>C)?

AlphaMissense predicts ambiguous (score 0.518) — an in-silico prediction, not a clinical call.

ATAD2 p.Arg393Pro

c.1178G>C · VCV4643625

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.518 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0265%, sas)

Computational evidence

Protein change
AlphaMissense	0.518	ambiguous
REVEL	0.573	indeterminate
SaProt	LLR -6.02	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.99 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 11 kb · p 0.0021 · regional, not allelic
Overall
CADD	25.5	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 0.0265% South Asian · 24/90,530 alleles

Filtering AF 0.0182% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0155%

Overall 0.00155% 25/1,611,698 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0265%	3,772
European (non-Finnish)	8.48e-05%	1,179,247

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: ATAD2
Protein: p.Arg393Pro
Coding: c.1178G>C
MANE Select: NM_014109
Type: single nucleotide variant
Location: chr8:123359665 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.63 · 120 PDB

Full ATAD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATAD2 p.Ala1155Val Uncertain significance ★ ⚠ same type
ATAD2 p.Ala329Thr Uncertain significance ★ ⚠ same type
ATAD2 p.Ala338Ser Uncertain significance ★ ⚠ same type
ATAD2 p.Ala499Gly Uncertain significance ★ ⚠ same type
ATAD2 p.Ala644Gly Uncertain significance ★ ⚠ same type
ATAD2 p.Ala771Pro Uncertain significance ★ ⚠ same type
ATAD2 p.Ala81Val Uncertain significance ★ ⚠ same type
ATAD2 p.Ala902Thr 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/atad2-p-arg393pro (accessed [today's date]).

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