Is ADARB1 p.Pro311Ala (c.931C>G) pathogenic?

ADARB1 p.Pro311Ala (c.931C>G) is classified Uncertain significance in ADARB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-21). AlphaMissense: likely benign (0.104); Very rare (popmax 6.85e-05%); Associated with Inborn genetic diseases.

What condition is associated with ADARB1 p.Pro311Ala (c.931C>G)?

ADARB1 p.Pro311Ala (c.931C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ADARB1 p.Pro311Ala (c.931C>G) in the general population?

ADARB1 p.Pro311Ala (c.931C>G) is very rare (popmax 6.85e-05%) (gnomAD).

What do computational predictors say about ADARB1 p.Pro311Ala (c.931C>G)?

AlphaMissense predicts likely benign (score 0.104) — an in-silico prediction, not a clinical call.

ADARB1 p.Pro311Ala

c.931C>G · VCV4568823

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.104 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.104	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -6.59	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 5.8	GERP 0.95, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 8,743 bp · p 0.0016 · regional, not allelic
Overall
CADD	22.0	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

Grpmax group 6.85e-05%

Overall 6.85e-05% 1/1,460,478 alleles · very rare

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: ADARB1
Protein: p.Pro311Ala
Coding: c.931C>G
MANE Select: NM_001112
Type: single nucleotide variant
Location: chr21:45176632 (GRCh38)
Gene constraint: LOEUF 0.323 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.12 · 13 PDB

Full ADARB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADARB1 p.Pro345Leu Uncertain significance ★★ ⚠ same condition
ADARB1 p.Ala497Thr Uncertain significance ★ ⚠ same condition
ADARB1 p.Ala608Thr Uncertain significance ★ ⚠ same condition
ADARB1 p.Arg20His Uncertain significance ★ ⚠ same condition
ADARB1 p.Arg244His Uncertain significance ★ ⚠ same condition
ADARB1 p.Arg287Gln Uncertain significance ★ ⚠ same condition
ADARB1 p.Arg287Leu Uncertain significance ★ ⚠ same condition
ADARB1 p.Arg329Cys Uncertain significance ★ ⚠ 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/adarb1-p-pro311ala (accessed [today's date]).

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