Is ATAD2B p.Ser706Arg (c.2118T>A) pathogenic?

ATAD2B p.Ser706Arg (c.2118T>A) is classified Uncertain significance in ATAD2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely benign (0.1602); Ultra-rare (popmax 0.0103%, amr).

How common is ATAD2B p.Ser706Arg (c.2118T>A) in the general population?

ATAD2B p.Ser706Arg (c.2118T>A) is ultra-rare (popmax 0.0103%, amr) (gnomAD).

What do computational predictors say about ATAD2B p.Ser706Arg (c.2118T>A)?

AlphaMissense predicts likely benign (score 0.1602) — an in-silico prediction, not a clinical call.

ATAD2B p.Ser706Arg

c.2118T>A · VCV3795081

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1602 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1602	likely benign
REVEL	0.17	moderately benign-leaning
SaProt	LLR -6.92	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 2.2	GERP -0.27, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 13 kb · p 0.0062 · regional, not allelic
Overall
CADD	15.35	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 0.0103% Admixed American · 6/58,440 alleles

Filtering AF 0.00438% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00301%

Overall 0.00118% 19/1,605,414 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0103%	9,740
South Asian	0.00443%	22,564
African / African-American	0.00135%	74,326
European (non-Finnish)	0.000681%	146,937

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: ATAD2B
Protein: p.Ser706Arg
Coding: c.2118T>A
MANE Select: NM_017552
Type: single nucleotide variant
Location: chr2:23823271 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.47 · 6 PDB

Full ATAD2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KLHL29 p.Ile706Val Uncertain significance ★ ⚠ same residue
ATAD2B p.Leu68= Benign ★★ same type
ATAD2B p.Ala1111Pro Uncertain significance ★ ⚠ same type
ATAD2B p.Ala1232Pro Uncertain significance ★ ⚠ same type
ATAD2B p.Ala1375Val Uncertain significance ★ ⚠ same type
ATAD2B p.Ala31Ser Uncertain significance ★ ⚠ same type
ATAD2B p.Ala50Asp Uncertain significance ★ ⚠ same type
ATAD2B p.Ala692Val 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/atad2b-p-ser706arg (accessed [today's date]).

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