Is ATAD2 p.Arg1367Cys (c.4099C>T) pathogenic?

ATAD2 p.Arg1367Cys (c.4099C>T) is classified Uncertain significance in ATAD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-08). AlphaMissense: ambiguous (0.4025); Very rare (popmax 0.00267%, afr).

How common is ATAD2 p.Arg1367Cys (c.4099C>T) in the general population?

ATAD2 p.Arg1367Cys (c.4099C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about ATAD2 p.Arg1367Cys (c.4099C>T)?

AlphaMissense predicts ambiguous (score 0.4025) — an in-silico prediction, not a clinical call.

ATAD2 p.Arg1367Cys

c.4099C>T · VCV3795059

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4025 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4025	ambiguous
REVEL	0.847	moderately pathogenic-leaning
SaProt	LLR -8.76	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 13 kb · p 0.94 · regional, not allelic
Overall
CADD	29.9	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 0.00267% African / African-American · 2/74,906 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000496% 8/1,613,664 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,453
European (non-Finnish)	0.000509%	196,641

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.Arg1367Cys
Coding: c.4099C>T
MANE Select: NM_014109
Type: single nucleotide variant
Location: chr8:123322970 (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-arg1367cys (accessed [today's date]).

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