Is DENND4B p.Gln901= (c.2703A>G) pathogenic?

DENND4B p.Gln901= (c.2703A>G) is classified Benign in DENND4B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-03-13). Rare (popmax 0.715%, afr); Associated with DENND4B-related disorder.

What condition is associated with DENND4B p.Gln901= (c.2703A>G)?

DENND4B p.Gln901= (c.2703A>G) is associated with DENND4B-related disorder (ClinVar).

How common is DENND4B p.Gln901= (c.2703A>G) in the general population?

DENND4B p.Gln901= (c.2703A>G) is rare (popmax 0.715%, afr) (gnomAD).

DENND4B p.Gln901=

c.2703A>G · rs2275483 · VCV3037524

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.715%, afr)

Conditions

DENND4B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	10.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.715% African / African-American · 468/65,410 alleles

Filtering AF 0.662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.641%

Overall 0.319% 4,082/1,280,628 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.715%	140
Admixed American	0.596%	168
East Asian	0.549%	182
South Asian	0.413%	242
Ashkenazi Jewishnot grpmax-eligible	0.293%	341
Remaining individualsnot grpmax-eligible	0.281%	356
European (non-Finnish)	0.268%	373
Middle Eastern	0.218%	459
Finnishnot grpmax-eligible	0.197%	507

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: DENND4B
Protein: p.Gln901=
Coding: c.2703A>G
MANE Select: NM_014856
dbSNP: rs2275483
Type: single nucleotide variant
Location: chr1:153934830 (GRCh38)
Gene constraint: LOEUF 0.527 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.32
Residue 901: the 'disordered' region

Full DENND4B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DENND4B-related disorder

Similar variants

DENND4B p.Val103Ile Uncertain significance ★★ ⚠ same condition
DENND4B p.Ala16Thr Uncertain significance ★ ⚠ same condition
DENND4B p.Leu440Val Uncertain significance ★ ⚠ same condition
DENND4B p.Val121Met Uncertain significance ⚠ same condition
DENND4B c.1819+4T>C Likely benign same condition
DENND4B c.2439+10C>T Likely benign same condition
DENND4B c.3624-6C>T Likely benign same condition
DENND4B c.4115-3C>T Likely benign same condition

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/dennd4b-p-gln901 (accessed [today's date]).

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