Is ATAD3A p.Arg342Ser (c.1024C>A) pathogenic?

ATAD3A p.Arg342Ser (c.1024C>A) is classified Uncertain significance in ATAD3A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.1568); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with ATAD3A p.Arg342Ser (c.1024C>A)?

ATAD3A p.Arg342Ser (c.1024C>A) is associated with Inborn genetic diseases (ClinVar).

How common is ATAD3A p.Arg342Ser (c.1024C>A) in the general population?

ATAD3A p.Arg342Ser (c.1024C>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about ATAD3A p.Arg342Ser (c.1024C>A)?

AlphaMissense predicts likely benign (score 0.1568) — an in-silico prediction, not a clinical call.

ATAD3A p.Arg342Ser

c.1024C>A · VCV4160855

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1568 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1568	likely benign
REVEL	0.251	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -1.9, phastCons 0.063
Regional constraint	o/e 0.94	unconstrained · MANE · 6,537 bp · p 0.3 · regional, not allelic
Overall
CADD	5.693	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R390S vs ClinVar R342S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,082 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000137% 2/1,461,734 alleles · very rare

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: ATAD3A
Protein: p.Arg342Ser
Coding: c.1024C>A
MANE Select: NM_001170535
Type: single nucleotide variant
Location: chr1:1523899 (GRCh38)
Gene constraint: LOEUF 0.861 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.35
Residue 342: a UniProt-annotated variant site (in phrinl)

Full ATAD3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ATAD3A p.Arg342Cys Uncertain significance ★★ ⚠ same residue
ATAD3A p.Arg342His Uncertain significance ★★ ⚠ same residue
ATAD3A p.Arg342Leu Uncertain significance ★ same residue
ATAD3A p.Arg342= Likely benign ★ same residue
ATAD3A p.Ala62Val Uncertain significance ★★ ⚠ same condition
ATAD3A p.Arg138Trp Uncertain significance ★★ same condition
ATAD3A p.Arg188Gln Uncertain significance ★★ ⚠ same condition
ATAD3A p.Arg208Cys Uncertain significance ★★ 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/atad3a-p-arg342ser (accessed [today's date]).

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