Is ADGB p.Lys892Thr (c.2675A>C) pathogenic?

ADGB p.Lys892Thr (c.2675A>C) is classified Uncertain significance in ADGB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-29). AlphaMissense: likely benign (0.1716); Absent from gnomAD v4.1.

How common is ADGB p.Lys892Thr (c.2675A>C) in the general population?

ADGB p.Lys892Thr (c.2675A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADGB p.Lys892Thr (c.2675A>C)?

AlphaMissense predicts likely benign (score 0.1716) — an in-silico prediction, not a clinical call.

ADGB p.Lys892Thr

c.2675A>C · rs2482731759 · VCV2607581

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1716 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1716	likely benign
REVEL	0.173	moderately benign-leaning
SaProt	LLR -6.16	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 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 216 kb · p 0.17 · regional, not allelic
Overall
CADD	17.52	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

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.Lys892Thr
Coding: c.2675A>C
MANE Select: NM_024694
dbSNP: rs2482731759
Type: single nucleotide variant
Location: chr6:146733911 (GRCh38)
Gene constraint: LOEUF 0.941 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.79

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-lys892thr (accessed [today's date]).

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