Is ATAD2 p.Pro49Ala (c.145C>G) pathogenic?

ATAD2 p.Pro49Ala (c.145C>G) is classified Uncertain significance in ATAD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely benign (0.0475); Very rare (popmax 0.00538%, afr).

How common is ATAD2 p.Pro49Ala (c.145C>G) in the general population?

ATAD2 p.Pro49Ala (c.145C>G) is very rare (popmax 0.00538%, afr) (gnomAD).

What do computational predictors say about ATAD2 p.Pro49Ala (c.145C>G)?

AlphaMissense predicts likely benign (score 0.0475) — an in-silico prediction, not a clinical call.

ATAD2 p.Pro49Ala

c.145C>G · VCV3440722

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0475 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00538%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0475	likely benign
REVEL	0.201	benign-leaning
SaProt	LLR -5.30	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 0.096	GERP -2.6
Regional constraint	o/e 0.99	unconstrained · MANE · 27 kb · p 0.83 · regional, not allelic
Overall
CADD	0.156	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 0.00538% African / African-American · 4/74,402 alleles

Filtering AF 0.00176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000377% 6/1,592,736 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00538%	18,600
Admixed American	0.00343%	29,117

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: ATAD2
Protein: p.Pro49Ala
Coding: c.145C>G
MANE Select: NM_014109
Type: single nucleotide variant
Location: chr8:123396213 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.63 · 120 PDB
Residue 49: the 'disordered' region

Full ATAD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATAD2 p.Ala1155Val Uncertain significance ★ ⚠ same type
ATAD2 p.Ala329Thr Uncertain significance ★ ⚠ same type
ATAD2 p.Ala338Ser Uncertain significance ★ ⚠ same type
ATAD2 p.Ala499Gly Uncertain significance ★ ⚠ same type
ATAD2 p.Ala644Gly Uncertain significance ★ ⚠ same type
ATAD2 p.Ala771Pro Uncertain significance ★ ⚠ same type
ATAD2 p.Ala81Val Uncertain significance ★ ⚠ same type
ATAD2 p.Ala902Thr 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/atad2-p-pro49ala (accessed [today's date]).

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