Is DENND4B p.Ser299= (c.897C>T) pathogenic?

DENND4B p.Ser299= (c.897C>T) is classified Likely benign in DENND4B (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-11-18). Very rare (popmax 0.00331%, nfe); Associated with DENND4B-related disorder.

What condition is associated with DENND4B p.Ser299= (c.897C>T)?

DENND4B p.Ser299= (c.897C>T) is associated with DENND4B-related disorder (ClinVar).

How common is DENND4B p.Ser299= (c.897C>T) in the general population?

DENND4B p.Ser299= (c.897C>T) is very rare (popmax 0.00331%, nfe) (gnomAD).

DENND4B p.Ser299=

c.897C>T · rs760755862 · VCV3053889

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00331%, nfe)

Conditions

DENND4B-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.399	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.7
Overall
CADD	2.038	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00331% European (non-Finnish) · 39/1,178,856 alleles

Filtering AF 0.00248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00217%

Overall 0.00254% 41/1,611,064 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00331%	30,227
African / African-American	0.00134%	74,866
South Asian	0.0011%	90,844

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.Ser299=
Coding: c.897C>T
MANE Select: NM_014856
dbSNP: rs760755862
Type: single nucleotide variant
Location: chr1:153942027 (GRCh38)
Gene constraint: LOEUF 0.527 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.32
Residue 299: the udenn domain

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-ser299 (accessed [today's date]).

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