Is ATAD3A p.Pro18Ser (c.52C>T) pathogenic?

ATAD3A p.Pro18Ser (c.52C>T) is classified Uncertain significance in ATAD3A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-11-24). AlphaMissense: likely benign (0.0672); Ultra-rare (popmax 0.0257%, eas).

How common is ATAD3A p.Pro18Ser (c.52C>T) in the general population?

ATAD3A p.Pro18Ser (c.52C>T) is ultra-rare (popmax 0.0257%, eas) (gnomAD).

What do computational predictors say about ATAD3A p.Pro18Ser (c.52C>T)?

AlphaMissense predicts likely benign (score 0.0672) — an in-silico prediction, not a clinical call.

ATAD3A p.Pro18Ser

c.52C>T · rs1413306192 · VCV2439306

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0672 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0257%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0672	likely benign
REVEL	0.087	moderately benign-leaning
SaProt	LLR -6.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.15	GERP -0.1
Regional constraint	o/e 0.73	unconstrained · MANE · 5,138 bp · p 0.00048 · regional, not allelic
Overall
CADD	16.65	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0257% East Asian · 8/31,124 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00933%

Overall 0.000644% 8/1,242,274 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.Pro18Ser
Coding: c.52C>T
MANE Select: NM_001170535
dbSNP: rs1413306192
Type: single nucleotide variant
Location: chr1:1512320 (GRCh38)
Gene constraint: LOEUF 0.861 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.35
Residue 18: the 'disordered' region; the 'required for interaction with the inner surface of the mitochondrial outer membrane' region

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

Similar variants

ATAD3A c.1266+1G>A Likely pathogenic ★★ same type
ATAD3A c.384+1G>A Likely pathogenic ★★ same type
ATAD3A p.Arg528Gln Likely pathogenic ★★ ⚠ same type
ATAD3A p.Arg528Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
ATAD3A c.282+5G>A Uncertain significance ★★ same type
ATAD3A c.283-3C>T Uncertain significance ★★ same type
ATAD3A c.385-3C>G Uncertain significance ★★ same type
ATAD3A p.Ala462Thr Uncertain significance ★★ ⚠ same type

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-pro18ser (accessed [today's date]).

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