Is ATAD2B p.Leu68= (c.202C>T) pathogenic?

ATAD2B p.Leu68= (c.202C>T) is classified Benign in ATAD2B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-07-22). Common (popmax 17.2%, mid) — too common for a highly-penetrant pathogenic allele.

ATAD2B p.Leu68=

Q: How common is ATAD2B p.Leu68= (c.202C>T) in the general population?

ATAD2B p.Leu68= (c.202C>T) is common (popmax 17.2%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.202C>T · rs61739076 · VCV1255163

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 17.2%, mid) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -2.6, phastCons 1
Overall
CADD	8.881	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 17.2% Middle Eastern · 986/5,738 alleles

Filtering AF 16.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.9%

Overall 12.5% 193,666/1,553,002 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	17.5%	6
Middle Easterngrpmax	17.2%	6
South Asian	14.2%	7
European (non-Finnish)	13.3%	8
Remaining individualsnot grpmax-eligible	13.2%	8
Finnishnot grpmax-eligible	9.29%	11
Amishnot grpmax-eligible	8.99%	11
Admixed American	7.87%	13
African / African-American	6.03%	17
East Asian	3.38%	30

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Leu68=
Coding: c.202C>T
MANE Select: NM_017552
dbSNP: rs61739076
Type: single nucleotide variant
Location: chr2:23926569 (GRCh38)
Gene constraint: LOEUF 0.376 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.47 · 6 PDB
Residue 68: the 'disordered' region

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

Similar variants

ATAD2B p.Leu68Val Uncertain significance ★ ⚠ same residue
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-leu68 (accessed [today's date]).

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