Is ATAD3A p.Arg129Ser (c.387G>C) pathogenic?

ATAD3A p.Arg129Ser (c.387G>C) is classified Uncertain significance in ATAD3A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-12). AlphaMissense: likely pathogenic (0.9181); Ultra-rare (popmax 0.0136%, eas); Associated with Inborn genetic diseases.

What condition is associated with ATAD3A p.Arg129Ser (c.387G>C)?

ATAD3A p.Arg129Ser (c.387G>C) is associated with Inborn genetic diseases (ClinVar).

How common is ATAD3A p.Arg129Ser (c.387G>C) in the general population?

ATAD3A p.Arg129Ser (c.387G>C) is ultra-rare (popmax 0.0136%, eas) (gnomAD).

What do computational predictors say about ATAD3A p.Arg129Ser (c.387G>C)?

AlphaMissense predicts likely pathogenic (score 0.9181) — an in-silico prediction, not a clinical call.

ATAD3A p.Arg129Ser

c.387G>C · rs1255854821 · VCV3130693

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9181 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0136%, eas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9181	likely pathogenic
REVEL	0.265	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 1.2, phastCons 1
Regional constraint	o/e 0.25	constrained · MANE · 364 bp · p 6.5e-05 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R177S vs ClinVar R129S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0136% East Asian · 6/44,190 alleles

Filtering AF 0.00586% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00399%

Overall 0.00042% 6/1,428,988 alleles · ultra-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.Arg129Ser
Coding: c.387G>C
MANE Select: NM_001170535
dbSNP: rs1255854821
Type: single nucleotide variant
Location: chr1:1517718 (GRCh38)
Gene constraint: LOEUF 0.861 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.35
Residue 129: the 'disordered' region

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.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
ATAD3A p.Arg212Cys Uncertain significance ★★ ⚠ same condition
ATAD3A p.Arg273Cys Uncertain significance ★★ ⚠ same condition
ATAD3A p.Arg327Gln Uncertain significance ★★ ⚠ same condition
ATAD3A p.Arg327Leu 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-arg129ser (accessed [today's date]).

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