Is ADRA1D p.Arg309Pro (c.926G>C) pathogenic?

ADRA1D p.Arg309Pro (c.926G>C) is classified Uncertain significance in ADRA1D (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-19). AlphaMissense: ambiguous (0.4666); Rare (popmax 0.148%, afr).

How common is ADRA1D p.Arg309Pro (c.926G>C) in the general population?

ADRA1D p.Arg309Pro (c.926G>C) is rare (popmax 0.148%, afr) (gnomAD).

What do computational predictors say about ADRA1D p.Arg309Pro (c.926G>C)?

AlphaMissense predicts ambiguous (score 0.4666) — an in-silico prediction, not a clinical call.

ADRA1D p.Arg309Pro

c.926G>C · rs191002054 · VCV3090761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4666 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.148%, afr)

Computational evidence

Protein change
AlphaMissense	0.4666	ambiguous
REVEL	0.376	indeterminate
SaProt	LLR -10.23	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP -0.29, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 27 kb · p 0.98 · regional, not allelic
Overall
CADD	26.8	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

Grpmax group 0.148% African / African-American · 108/73,168 alleles

Filtering AF 0.125% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.117%

Overall 0.00908% 141/1,553,038 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.148%	677
Admixed American	0.0275%	3,637
Remaining individualsnot grpmax-eligible	0.0133%	7,515
European (non-Finnish)	0.000957%	104,440

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: ADRA1D
Protein: p.Arg309Pro
Coding: c.926G>C
MANE Select: NM_000678
dbSNP: rs191002054
Type: single nucleotide variant
Location: chr20:4248032 (GRCh38)
Gene constraint: LOEUF 1.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.88

Full ADRA1D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADRA1D p.Ala174Val Uncertain significance ★ ⚠ same type
ADRA1D p.Ala20Gly Uncertain significance ★ ⚠ same type
ADRA1D p.Ala20Thr Uncertain significance ★ ⚠ same type
ADRA1D p.Ala218Val Uncertain significance ★ ⚠ same type
ADRA1D p.Ala255Pro Uncertain significance ★ ⚠ same type
ADRA1D p.Ala35Gly Uncertain significance ★ ⚠ same type
ADRA1D p.Ala36Gly Uncertain significance ★ ⚠ same type
ADRA1D p.Ala42Pro 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/adra1d-p-arg309pro (accessed [today's date]).

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