Is ATAD5 p.Arg1502Trp (c.4504C>T) pathogenic?

ATAD5 p.Arg1502Trp (c.4504C>T) is classified Uncertain significance in ATAD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely benign (0.1038); Ultra-rare (popmax 0.0559%, eas).

How common is ATAD5 p.Arg1502Trp (c.4504C>T) in the general population?

ATAD5 p.Arg1502Trp (c.4504C>T) is ultra-rare (popmax 0.0559%, eas) (gnomAD).

What do computational predictors say about ATAD5 p.Arg1502Trp (c.4504C>T)?

AlphaMissense predicts likely benign (score 0.1038) — an in-silico prediction, not a clinical call.

ATAD5 p.Arg1502Trp

c.4504C>T · VCV3441939

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1038 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0559%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1038	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -8.01	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 0.95, phastCons 0.036
Regional constraint	o/e 0.81	unconstrained · MANE · 7,569 bp · p 3.5e-05 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0559% East Asian · 25/44,754 alleles

Filtering AF 0.0388% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0331%

Overall 0.00295% 47/1,594,372 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0559%	1,790
Admixed American	0.00542%	18,442
European (non-Finnish)	0.00154%	65,134
African / African-American	0.00135%	73,812

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: ATAD5
Protein: p.Arg1502Trp
Coding: c.4504C>T
MANE Select: NM_024857
Type: single nucleotide variant
Location: chr17:30893357 (GRCh38)
Gene constraint: LOEUF 0.417 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.76 · 4 PDB
Residue 1502: a turn

Full ATAD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATAD5 c.4013-8G>A Benign ★★ same type
ATAD5 p.Asp826= Likely benign ★★ same type
ATAD5 p.Ala1326Thr Uncertain significance ★ ⚠ same type
ATAD5 p.Ala1459Thr Uncertain significance ★ ⚠ same type
ATAD5 p.Ala1539Pro Uncertain significance ★ ⚠ same type
ATAD5 p.Ala1711Val Uncertain significance ★ ⚠ same type
ATAD5 p.Ala326Val Uncertain significance ★ ⚠ same type
ATAD5 p.Ala414Thr 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/atad5-p-arg1502trp (accessed [today's date]).

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