Is DENR p.Gln96Pro (c.287A>C) pathogenic?

DENR p.Gln96Pro (c.287A>C) is classified Uncertain significance in DENR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-27). AlphaMissense: likely pathogenic (0.9741); Absent from gnomAD v4.1.

How common is DENR p.Gln96Pro (c.287A>C) in the general population?

DENR p.Gln96Pro (c.287A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DENR p.Gln96Pro (c.287A>C)?

AlphaMissense predicts likely pathogenic (score 0.9741) — an in-silico prediction, not a clinical call.

DENR p.Gln96Pro

c.287A>C · VCV3501117

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9741 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9741	likely pathogenic
REVEL	0.344	indeterminate
SaProt	LLR -5.25	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 2.3, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 14 kb · p 0.0035 · regional, not allelic
Overall
CADD	22.7	PHRED · no single calibrated threshold — expert panels disagree

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: DENR
Protein: p.Gln96Pro
Coding: c.287A>C
MANE Select: NM_003677
Type: single nucleotide variant
Location: chr12:122765379 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.92 (gnomAD)
Structure: AlphaFold pLDDT 63.04 · 5 PDB
Residue 96: the 'disordered' region

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

Similar variants

DENR p.Ala21Val Uncertain significance ★ ⚠ same type
DENR p.Asp186Glu Uncertain significance ★ ⚠ same type
DENR p.Asp26Tyr Uncertain significance ★ ⚠ same type
DENR p.Glu77Ala Uncertain significance ★ ⚠ same type
DENR p.Glu89Asp Uncertain significance ★ ⚠ same type
DENR p.Glu89Lys Uncertain significance ★ ⚠ same type
DENR p.Gly194Arg Uncertain significance ★ ⚠ same type
DENR p.Leu32Pro 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/denr-p-gln96pro (accessed [today's date]).

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