Is DENND2A p.Pro311Ser (c.931C>T) pathogenic?

DENND2A p.Pro311Ser (c.931C>T) is classified Uncertain significance in DENND2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). AlphaMissense: likely benign (0.2722); Absent from gnomAD v4.1.

How common is DENND2A p.Pro311Ser (c.931C>T) in the general population?

DENND2A p.Pro311Ser (c.931C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DENND2A p.Pro311Ser (c.931C>T)?

AlphaMissense predicts likely benign (score 0.2722) — an in-silico prediction, not a clinical call.

DENND2A p.Pro311Ser

c.931C>T · VCV3500922

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2722 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2722	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -7.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 5.3, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 17 kb · p 0.62 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DENND2A
Protein: p.Pro311Ser
Coding: c.931C>T
MANE Select: NM_015689
Type: single nucleotide variant
Location: chr7:140601467 (GRCh38)
Gene constraint: LOEUF 0.632 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.16
Residue 311: the 'disordered' region

Full DENND2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DENND2A c.1779+8G>A Uncertain significance ★ same type
DENND2A p.Ala276Gly Uncertain significance ★ ⚠ same type
DENND2A p.Ala422Val Uncertain significance ★ ⚠ same type
DENND2A p.Ala68Thr Uncertain significance ★ ⚠ same type
DENND2A p.Ala784Glu Uncertain significance ★ ⚠ same type
DENND2A p.Ala784Thr Uncertain significance ★ ⚠ same type
DENND2A p.Arg110Ser Uncertain significance ★ ⚠ same type
DENND2A p.Arg141Gln 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/dennd2a-p-pro311ser (accessed [today's date]).

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