Is ATAD2 p.Ser764Pro (c.2290T>C) pathogenic?

ATAD2 p.Ser764Pro (c.2290T>C) is classified Uncertain significance in ATAD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely benign (0.0675); Very rare (popmax 0.00466%, sas).

How common is ATAD2 p.Ser764Pro (c.2290T>C) in the general population?

ATAD2 p.Ser764Pro (c.2290T>C) is very rare (popmax 0.00466%, sas) (gnomAD).

What do computational predictors say about ATAD2 p.Ser764Pro (c.2290T>C)?

AlphaMissense predicts likely benign (score 0.0675) — an in-silico prediction, not a clinical call.

ATAD2 p.Ser764Pro

c.2290T>C · rs1358342322 · VCV3130644

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0675 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00466%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0675	likely benign
REVEL	0.16	moderately benign-leaning
SaProt	LLR -7.07	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 3	GERP -2.2, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 23 kb · p 2.4e-11 · regional, not allelic
Overall
CADD	17.52	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 0.00466% South Asian · 4/85,860 alleles

Filtering AF 0.00159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000933%

Overall 0.000692% 11/1,588,902 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00466%	21,465
European (non-Finnish)	0.0006%	166,592

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.Ser764Pro
Coding: c.2290T>C
MANE Select: NM_014109
dbSNP: rs1358342322
Type: single nucleotide variant
Location: chr8:123346673 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.63 · 120 PDB

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-ser764pro (accessed [today's date]).

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