Is ADGB p.Trp1475Cys (c.4425G>T) pathogenic?

ADGB p.Trp1475Cys (c.4425G>T) is classified Uncertain significance in ADGB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely pathogenic (0.8069); Absent from gnomAD v4.1.

How common is ADGB p.Trp1475Cys (c.4425G>T) in the general population?

ADGB p.Trp1475Cys (c.4425G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADGB p.Trp1475Cys (c.4425G>T)?

AlphaMissense predicts likely pathogenic (score 0.8069) — an in-silico prediction, not a clinical call.

ADGB p.Trp1475Cys

c.4425G>T · VCV4013529

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8069 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8069	likely pathogenic
REVEL	0.216	benign-leaning
SaProt	LLR -6.37	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 216 kb · p 0.17 · regional, not allelic
Overall
CADD	23.3	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: ADGB
Protein: p.Trp1475Cys
Coding: c.4425G>T
MANE Select: NM_024694
Type: single nucleotide variant
Location: chr6:146788498 (GRCh38)
Gene constraint: LOEUF 0.941 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.79
Residue 1475: a UniProt-annotated variant site (found in a patient with asthenozoospermia; likely pathogenic; no effect on interaction with calmodulin); the 'disordered' region

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

Similar variants

ADGB p.Ile645= Likely benign ★★ same type
ADGB p.Ala1104Asp Uncertain significance ★ ⚠ same type
ADGB p.Ala1104Gly Uncertain significance ★ ⚠ same type
ADGB p.Ala1339Val Uncertain significance ★ ⚠ same type
ADGB p.Ala1443Glu Uncertain significance ★ ⚠ same type
ADGB p.Ala145Glu Uncertain significance ★ ⚠ same type
ADGB p.Ala1567Glu Uncertain significance ★ ⚠ same type
ADGB p.Ala1630Gly 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/adgb-p-trp1475cys (accessed [today's date]).

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