Is ADRA1B p.Ser402Trp (c.1205C>G) pathogenic?

ADRA1B p.Ser402Trp (c.1205C>G) is classified Uncertain significance in ADRA1B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-03). AlphaMissense: likely benign (0.1991); Very rare (popmax 0.00153%, afr).

How common is ADRA1B p.Ser402Trp (c.1205C>G) in the general population?

ADRA1B p.Ser402Trp (c.1205C>G) is very rare (popmax 0.00153%, afr) (gnomAD).

What do computational predictors say about ADRA1B p.Ser402Trp (c.1205C>G)?

AlphaMissense predicts likely benign (score 0.1991) — an in-silico prediction, not a clinical call.

ADRA1B p.Ser402Trp

c.1205C>G · VCV3838990

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1991 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00153%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1991	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -9.79	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 5.4	GERP 1.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 426 bp · p 0.082 · regional, not allelic
Overall
CADD	31.0	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 0.00153% African / African-American · 1/65,290 alleles

Filtering AF 0.000209% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000525% 7/1,334,308 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00153%	65,290
European (non-Finnish)	0.000581%	172,123

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: ADRA1B
Protein: p.Ser402Trp
Coding: c.1205C>G
MANE Select: NM_000679
Type: single nucleotide variant
Location: chr5:159972134 (GRCh38)
Gene constraint: LOEUF 1.449 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.95
Residue 402: the 'disordered' region

Full ADRA1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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ADRA1B p.Ala217Val Uncertain significance ★ ⚠ same type
ADRA1B p.Ala449Thr Uncertain significance ★ ⚠ same type
ADRA1B p.Ala503Thr Uncertain significance ★ ⚠ same type
ADRA1B p.Ala516Glu Uncertain significance ★ ⚠ same type
ADRA1B p.Ala54Pro Uncertain significance ★ ⚠ same type
ADRA1B p.Ala90Asp Uncertain significance ★ ⚠ same type
ADRA1B p.Arg115Gln 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/adra1b-p-ser402trp (accessed [today's date]).

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