Is ATAD3A p.Pro311Arg (c.932C>G) pathogenic?

ATAD3A p.Pro311Arg (c.932C>G) is classified Uncertain significance in ATAD3A (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-20). AlphaMissense: likely benign (0.1942); Very rare (popmax 0.00935%, afr); Associated with Harel-Yoon syndrome.

What condition is associated with ATAD3A p.Pro311Arg (c.932C>G)?

ATAD3A p.Pro311Arg (c.932C>G) is associated with Harel-Yoon syndrome (ClinVar).

How common is ATAD3A p.Pro311Arg (c.932C>G) in the general population?

ATAD3A p.Pro311Arg (c.932C>G) is very rare (popmax 0.00935%, afr) (gnomAD).

What do computational predictors say about ATAD3A p.Pro311Arg (c.932C>G)?

AlphaMissense predicts likely benign (score 0.1942) — an in-silico prediction, not a clinical call.

ATAD3A p.Pro311Arg

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.932C>G · rs767934619 · VCV1696578

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1942 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00935%, afr)

Conditions

Harel-Yoon syndrome

Computational evidence

Protein change
AlphaMissense	0.1942	likely benign
REVEL	0.447	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 6,537 bp · p 0.3 · regional, not allelic
Overall
CADD	22.5	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 P359R vs ClinVar P311R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00935% African / African-American · 7/74,876 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000496% 8/1,612,810 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00935%	10,697
Remaining individualsnot grpmax-eligible	0.0016%	62,386

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.Pro311Arg
Coding: c.932C>G
MANE Select: NM_001170535
dbSNP: rs767934619
Type: single nucleotide variant
Location: chr1:1523536 (GRCh38)
Gene constraint: LOEUF 0.861 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.35
Residue 311: 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.Pro311Ser Benign ★★ same residue
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

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-pro311arg (accessed [today's date]).

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