Is DOP1B p.Arg994Pro (c.2981G>C) pathogenic?

DOP1B p.Arg994Pro (c.2981G>C) is classified Uncertain significance in DOP1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely pathogenic (0.9716); Absent from gnomAD v4.1.

How common is DOP1B p.Arg994Pro (c.2981G>C) in the general population?

DOP1B p.Arg994Pro (c.2981G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOP1B p.Arg994Pro (c.2981G>C)?

AlphaMissense predicts likely pathogenic (score 0.9716) — an in-silico prediction, not a clinical call.

DOP1B p.Arg994Pro

c.2981G>C · VCV4661864

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9716 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9716	likely pathogenic · top 4% in DOP1B
REVEL	0.804	moderately pathogenic-leaning
SaProt	LLR -9.97	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 129 kb · p 0.0008 · regional, not allelic
Overall
CADD	28.9	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: DOP1B
Protein: p.Arg994Pro
Coding: c.2981G>C
MANE Select: NM_001320714
Type: single nucleotide variant
Location: chr21:36239869 (GRCh38)
Gene constraint: LOEUF 0.831 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.36

Full DOP1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOP1B p.Ile343Met Uncertain significance ★★ ⚠ same type
DOP1B p.Pro1079Ser Uncertain significance ★★ ⚠ same type
DOP1B p.Val124Leu Uncertain significance ★★ ⚠ same type
DOP1B p.Ala2159= Benign ★★ same type
DOP1B p.Ala649Val Benign ★★ same type
DOP1B p.Ala969= Benign ★★ same type
DOP1B p.Arg1938His Benign ★★ same type
DOP1B p.Asn726= Benign/Likely benign ★★ 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/dop1b-p-arg994pro (accessed [today's date]).

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