Is ATAD3A p.Ser584Phe (c.1751C>T) pathogenic?

ATAD3A p.Ser584Phe (c.1751C>T) is classified Uncertain significance in ATAD3A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-13). AlphaMissense: likely benign (0.075); Ultra-rare (popmax 0.012%, afr); Associated with Inborn genetic diseases.

What condition is associated with ATAD3A p.Ser584Phe (c.1751C>T)?

ATAD3A p.Ser584Phe (c.1751C>T) is associated with Inborn genetic diseases, Harel-Yoon syndrome (ClinVar).

How common is ATAD3A p.Ser584Phe (c.1751C>T) in the general population?

ATAD3A p.Ser584Phe (c.1751C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about ATAD3A p.Ser584Phe (c.1751C>T)?

AlphaMissense predicts likely benign (score 0.075) — an in-silico prediction, not a clinical call.

ATAD3A p.Ser584Phe

c.1751C>T · rs770924627 · VCV1342411

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.075 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.075	likely benign
REVEL	0.302	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -2
Regional constraint	o/e 0.90	unconstrained · MANE · 9,713 bp · p 0.11 · regional, not allelic
Overall
CADD	0.002	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 S632F vs ClinVar S584F) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,860 alleles

Filtering AF 0.00624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00124% 20/1,612,582 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,318
Admixed American	0.00667%	14,993
European (non-Finnish)	0.000593%	168,513

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.Ser584Phe
Coding: c.1751C>T
MANE Select: NM_001170535
dbSNP: rs770924627
Type: single nucleotide variant
Location: chr1:1534062 (GRCh38)
Gene constraint: LOEUF 0.861 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.35
Residue 584: 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

Also linked: Harel-Yoon syndrome

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.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

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-ser584phe (accessed [today's date]).

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