Is ADAM15 p.Pro769= (c.2307C>T) pathogenic?

ADAM15 p.Pro769= (c.2307C>T) is classified Uncertain significance in ADAM15 (ClinVar, No assertion criteria, 1 submitter). Absent from gnomAD v4.1.

How common is ADAM15 p.Pro769= (c.2307C>T) in the general population?

ADAM15 p.Pro769= (c.2307C>T) is absent from gnomAD v4.1 (gnomAD).

ADAM15 p.Pro769=

c.2307C>T · rs483352774 · VCV100897

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.052	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.7	GERP 1.4, phastCons 1
Overall
CADD	14.81	PHRED · no single calibrated threshold — expert panels disagree

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: ADAM15
Protein: p.Pro769=
Coding: c.2307C>T
MANE Select: NM_207197
dbSNP: rs483352774
Type: single nucleotide variant
Location: chr1:155061444 (GRCh38)
Gene constraint: LOEUF 0.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.35
Residue 769: the 'disordered' region

Full ADAM15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAM15 c.1918-6G>T Benign ★★ same type
ADAM15 p.Arg268His Likely benign ★★ ⚠ same type
ADAM15 p.Leu240Met Benign ★★ same type
ADAM15 p.Ala221Asp Uncertain significance ★ ⚠ same type
ADAM15 p.Ala301Val Uncertain significance ★ ⚠ same type
ADAM15 p.Ala343Thr Uncertain significance ★ ⚠ same type
ADAM15 p.Ala347Ser Uncertain significance ★ ⚠ same type
ADAM15 p.Ala39Thr 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/adam15-p-pro769 (accessed [today's date]).

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