Is ATAD3A p.Ala172Asp (c.515C>A) pathogenic?

ATAD3A p.Ala172Asp (c.515C>A) is classified Uncertain significance in ATAD3A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-14). AlphaMissense: ambiguous (0.418); Very rare (popmax 0.00133%, afr).

How common is ATAD3A p.Ala172Asp (c.515C>A) in the general population?

ATAD3A p.Ala172Asp (c.515C>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ATAD3A p.Ala172Asp (c.515C>A)?

AlphaMissense predicts ambiguous (score 0.418) — an in-silico prediction, not a clinical call.

ATAD3A p.Ala172Asp

c.515C>A · VCV4529933

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.418 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
AlphaMissense	0.418	ambiguous
REVEL	0.231	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 6,537 bp · p 0.3 · regional, not allelic
Overall
CADD	25.0	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 A220D vs ClinVar A172D) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,980 alleles

Overall 6.86e-05% 1/1,457,170 alleles · very 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.Ala172Asp
Coding: c.515C>A
MANE Select: NM_001170535
Type: single nucleotide variant
Location: chr1:1520141 (GRCh38)
Gene constraint: LOEUF 0.861 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.35
Residue 172: a UniProt-annotated variant site (in phrinl)

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-ala172asp (accessed [today's date]).

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