Is ATAD5 p.Arg52= (c.154A>C) pathogenic?

ATAD5 p.Arg52= (c.154A>C) is classified Likely benign in ATAD5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-17). Rare (popmax 0.363%, mid); Associated with ATAD5-related disorder.

What condition is associated with ATAD5 p.Arg52= (c.154A>C)?

ATAD5 p.Arg52= (c.154A>C) is associated with ATAD5-related disorder (ClinVar).

How common is ATAD5 p.Arg52= (c.154A>C) in the general population?

ATAD5 p.Arg52= (c.154A>C) is rare (popmax 0.363%, mid) (gnomAD).

ATAD5 p.Arg52=

c.154A>C · rs139839085 · VCV3041965

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.363%, mid)

Conditions

ATAD5-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8	GERP 1.8, phastCons 1
Overall
CADD	10.26	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.363% Middle Eastern · 22/6,054 alleles

Filtering AF 0.246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.208%

Overall 0.0361% 583/1,613,192 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.363%	275
Ashkenazi Jewishnot grpmax-eligible	0.172%	580
South Asian	0.0892%	1,121
Remaining individualsnot grpmax-eligible	0.0592%	1,688
Admixed American	0.0568%	1,760
Finnishnot grpmax-eligible	0.0484%	2,065
European (non-Finnish)	0.0274%	3,652
African / African-American	0.00533%	18,753

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.Arg52=
Coding: c.154A>C
MANE Select: NM_024857
dbSNP: rs139839085
Type: single nucleotide variant
Location: chr17:30834235 (GRCh38)
Gene constraint: LOEUF 0.417 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 46.76 · 4 PDB

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

Disease context

ATAD5-related disorder

Similar variants

ATAD5 c.2956+9T>C Likely benign same condition
ATAD5 c.5456+7G>C Benign same condition
ATAD5 c.5457-7T>G Likely benign same condition
ATAD5 p.Arg1448Cys Benign same condition
ATAD5 p.Arg249Lys Benign same condition
ATAD5 p.Asn1767Ser Benign same condition
ATAD5 p.Asn699His Benign ⚠ same condition
ATAD5 p.Asp140Asn Likely benign same condition

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-arg52 (accessed [today's date]).

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