Is ATAD2B p.Val85Ile (c.253G>A) pathogenic?

ATAD2B p.Val85Ile (c.253G>A) is classified Uncertain significance in ATAD2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-24). AlphaMissense: likely benign (0.0623); Very rare (popmax 0.00334%, amr).

How common is ATAD2B p.Val85Ile (c.253G>A) in the general population?

ATAD2B p.Val85Ile (c.253G>A) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about ATAD2B p.Val85Ile (c.253G>A)?

AlphaMissense predicts likely benign (score 0.0623) — an in-silico prediction, not a clinical call.

ATAD2B p.Val85Ile

c.253G>A · VCV3795154

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0623 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0623	likely benign
REVEL	0.148	moderately benign-leaning
SaProt	LLR -6.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.44 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.55	GERP -0.21, phastCons 0.087
Regional constraint	o/e 1.02	unconstrained · MANE · 39 kb · p 0.77 · regional, not allelic
Overall
CADD	15.02	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 0.00334% Admixed American · 2/59,966 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000205% 3/1,460,834 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,983
European (non-Finnish)	8.48e-05%	1,179,290

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.Val85Ile
Coding: c.253G>A
MANE Select: NM_017552
Type: single nucleotide variant
Location: chr2:23895934 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.47 · 6 PDB
Residue 85: the 'disordered' region

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

Similar variants

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
ATAD2B p.Ala975Thr 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-val85ile (accessed [today's date]).

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