Is DENND4B p.Pro1012= (c.3036G>A) pathogenic?

DENND4B p.Pro1012= (c.3036G>A) is classified Likely benign in DENND4B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-27). Rare (popmax 0.213%, afr); Associated with DENND4B-related disorder.

What condition is associated with DENND4B p.Pro1012= (c.3036G>A)?

DENND4B p.Pro1012= (c.3036G>A) is associated with DENND4B-related disorder (ClinVar).

How common is DENND4B p.Pro1012= (c.3036G>A) in the general population?

DENND4B p.Pro1012= (c.3036G>A) is rare (popmax 0.213%, afr) (gnomAD).

DENND4B p.Pro1012=

c.3036G>A · rs370527955 · VCV3048357

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.213%, afr)

Conditions

DENND4B-related disorder

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 -9.1
Overall
CADD	0.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.213% African / African-American · 160/74,988 alleles

Filtering AF 0.186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.176%

Overall 0.0114% 183/1,610,076 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.213%	469
Admixed American	0.0118%	8,494
Remaining individualsnot grpmax-eligible	0.0112%	8,900
South Asian	0.00221%	45,245
European (non-Finnish)	0.000594%	168,367

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.Pro1012=
Coding: c.3036G>A
MANE Select: NM_014856
dbSNP: rs370527955
Type: single nucleotide variant
Location: chr1:153933777 (GRCh38)
Gene constraint: LOEUF 0.527 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.32
Residue 1012: 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.Pro1012Leu Uncertain significance ★ ⚠ same residue
DENND4B p.Pro1012Thr Uncertain significance ★ ⚠ same residue
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

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-pro1012 (accessed [today's date]).

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