Is OTUD7B p.Pro701= (c.2103G>T) pathogenic?

OTUD7B p.Pro701= (c.2103G>T) is classified Benign in OTUD7B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-23). Common (popmax 6.6%, afr) — too common for a highly-penetrant pathogenic allele.

OTUD7B p.Pro701=

Q: How common is OTUD7B p.Pro701= (c.2103G>T) in the general population?

OTUD7B p.Pro701= (c.2103G>T) is common (popmax 6.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2103G>T · rs56929499 · VCV791609

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.6%, afr) — 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 0.58	GERP -0.69, phastCons 0.45
Overall
CADD	1.209	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.6% African / African-American · 4,950/74,974 alleles

Filtering AF 6.45% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.39%

Overall 0.403% 6,493/1,610,142 alleles · common exomes 3,423/1,457,876 · genomes 3,070/152,266 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.6%	15
Middle Eastern	0.846%	118
Admixed American	0.756%	132
Remaining individualsnot grpmax-eligible	0.606%	165
European (non-Finnish)	0.054%	1,852
South Asian	0.0287%	3,483

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: OTUD7B
Protein: p.Pro701=
Coding: c.2103G>T
MANE Select: NM_020205
dbSNP: rs56929499
Type: single nucleotide variant
Location: chr1:149944286 (GRCh38)
Gene constraint: LOEUF 0.526 · pLI 0.87 (gnomAD)
Structure: AlphaFold pLDDT 67.63 · 3 PDB
Residue 701: the 'disordered' region

Full OTUD7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

OTUD7B p.Asp407= Benign ★★ same type
OTUD7B p.Gly59= Benign ★★ same type
OTUD7B p.Ala278Thr Uncertain significance ★ ⚠ same type
OTUD7B p.Ala303Thr Uncertain significance ★ ⚠ same type
OTUD7B p.Ala342Val Uncertain significance ★ ⚠ same type
OTUD7B p.Ala361Ser Uncertain significance ★ ⚠ same type
OTUD7B p.Ala452Thr Uncertain significance ★ ⚠ same type
OTUD7B p.Arg111Gln 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/otud7b-p-pro701 (accessed [today's date]).

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