Is ATAD3A p.Ala561Phe (c.1680_1682delinsCTT) pathogenic?

ATAD3A p.Ala561Phe (c.16801682delinsCTT) is classified Uncertain significance in ATAD3A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-19). Absent from gnomAD; Associated with pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal.

How common is ATAD3A p.Ala561Phe (c.1680_1682delinsCTT) in the general population?

ATAD3A p.Ala561Phe (c.1680_1682delinsCTT) is absent from gnomAD (gnomAD).

ATAD3A p.Ala561Phe

Q: What condition is associated with ATAD3A p.Ala561Phe (c.1680_1682delinsCTT)?

ATAD3A p.Ala561Phe (c.1680_1682delinsCTT) is associated with pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal, Harel-Yoon syndrome (ClinVar).

c.1680_1682delinsCTT · rs2520918797 · VCV2664325

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -12	GERP -2.5
Regional constraint	o/e 0.90	unconstrained · MANE · 9,713 bp · p 0.11 · regional, not allelic
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ATAD3A
Protein: p.Ala561Phe
Coding: c.1680_1682delinsCTT
MANE Select: NM_001170535
dbSNP: rs2520918797
Type: Indel
Location: chr1:1533991 (GRCh38)
Gene constraint: LOEUF 0.861 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.35
Residue 561: a UniProt-annotated variant site (in phrinl)

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

Disease context

pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Harel-Yoon syndrome

Similar variants

ATAD3A p.Tyr70fs Likely pathogenic ★ same condition
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 c.385-3C>G Uncertain significance ★★ same condition
ATAD3A p.Ala462Thr Uncertain significance ★★ ⚠ same condition
ATAD3A p.Arg138Trp Uncertain significance ★★ same condition
ATAD3A p.Arg273Ser 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-ala561phe (accessed [today's date]).

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