Is ADAM8 p.Ala63= (c.189C>G) pathogenic?

ADAM8 p.Ala63= (c.189C>G) is classified Likely benign in ADAM8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). Very rare (popmax 6.96e-05%).

How common is ADAM8 p.Ala63= (c.189C>G) in the general population?

ADAM8 p.Ala63= (c.189C>G) is very rare (popmax 6.96e-05%) (gnomAD).

ADAM8 p.Ala63=

c.189C>G · VCV3488572

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.96e-05%)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.046	GERP -2.7
Overall
CADD	1.847	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.96e-05%

Overall 6.96e-05% 1/1,436,262 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: ADAM8
Protein: p.Ala63=
Coding: c.189C>G
MANE Select: NM_001109
Type: single nucleotide variant
Location: chr10:133274197 (GRCh38)
Gene constraint: LOEUF 1.423 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.28 · 1 PDB

Full ADAM8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAM8 p.Ala118= Benign ★★ same type
ADAM8 p.Ala490Thr Benign ★★ same type
ADAM8 p.Arg36His Benign ★★ ⚠ same type
ADAM8 p.Arg433Cys Benign ★★ ⚠ same type
ADAM8 c.228-2A>G Uncertain significance ★ same type
ADAM8 p.Ala119Ser Uncertain significance ★ ⚠ same type
ADAM8 p.Ala119Thr Uncertain significance ★ ⚠ same type
ADAM8 p.Ala164Ser 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/adam8-p-ala63 (accessed [today's date]).

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