Is ADAM8 p.Pro782= (c.2346A>G) pathogenic?

ADAM8 p.Pro782= (c.2346A>G) is classified Likely benign in ADAM8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). Ultra-rare (popmax 0.055%, amr).

How common is ADAM8 p.Pro782= (c.2346A>G) in the general population?

ADAM8 p.Pro782= (c.2346A>G) is ultra-rare (popmax 0.055%, amr) (gnomAD).

ADAM8 p.Pro782=

c.2346A>G · VCV4637463

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.055%, amr)

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 -20	GERP -2.5
Overall
CADD	0.069	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.055% Admixed American · 28/50,936 alleles

Filtering AF 0.0391% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0336%

Overall 0.00183% 28/1,532,880 alleles · ultra-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.Pro782=
Coding: c.2346A>G
MANE Select: NM_001109
Type: single nucleotide variant
Location: chr10:133263739 (GRCh38)
Gene constraint: LOEUF 1.423 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.28 · 1 PDB
Residue 782: the 'disordered' region

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-pro782 (accessed [today's date]).

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