Is ATAD3A p.Arg329His (c.986G>A) pathogenic?

ATAD3A p.Arg329His (c.986G>A) is classified Uncertain significance in ATAD3A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-05). AlphaMissense: ambiguous (0.4688); Very rare (popmax 0.00133%, afr); Associated with Harel-Yoon syndrome.

What condition is associated with ATAD3A p.Arg329His (c.986G>A)?

ATAD3A p.Arg329His (c.986G>A) is associated with Harel-Yoon syndrome (ClinVar).

How common is ATAD3A p.Arg329His (c.986G>A) in the general population?

ATAD3A p.Arg329His (c.986G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ATAD3A p.Arg329His (c.986G>A)?

AlphaMissense predicts ambiguous (score 0.4688) — an in-silico prediction, not a clinical call.

ATAD3A p.Arg329His

Q: How is Ocular anomalies-axonal neuropathy-developmental delay syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.986G>A · rs1641699576 · VCV1199194

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4688 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

Harel-Yoon syndrome

Computational evidence

Protein change
AlphaMissense	0.4688	ambiguous
REVEL	0.655	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 6,537 bp · p 0.3 · regional, not allelic
Overall
CADD	25.3	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 R377H vs ClinVar R329H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,926 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000372% 6/1,613,892 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,926
South Asian	0.0011%	91,088
European (non-Finnish)	0.000339%	295,002

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.Arg329His
Coding: c.986G>A
MANE Select: NM_001170535
dbSNP: rs1641699576
Type: single nucleotide variant
Location: chr1:1523861 (GRCh38)
Gene constraint: LOEUF 0.861 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.35
Residue 329: a UniProt-annotated variant site (in phrinl)

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

Disease context

Harel-Yoon syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Ocular anomalies-axonal neuropathy-developmental delay syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

ATAD3A p.Arg528Gln Likely pathogenic ★★ ⚠ same condition
ATAD3A p.Arg528Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
ATAD3A c.283-3C>T Uncertain significance ★★ same condition
ATAD3A p.Arg138Trp Uncertain significance ★★ same condition
ATAD3A p.Arg273Ser Uncertain significance ★★ ⚠ same condition
ATAD3A p.Arg342His Uncertain significance ★★ ⚠ same condition
ATAD3A p.Glu545Lys Uncertain significance ★★ same condition
ATAD3A p.Leu437Gln 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-arg329his (accessed [today's date]).

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