Is ADAM15 p.Arg796Pro (c.2387G>C) pathogenic?

ADAM15 p.Arg796Pro (c.2387G>C) is classified Uncertain significance in ADAM15 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-06). AlphaMissense: likely benign (0.3285); Ultra-rare (popmax 0.0336%, mid).

How common is ADAM15 p.Arg796Pro (c.2387G>C) in the general population?

ADAM15 p.Arg796Pro (c.2387G>C) is ultra-rare (popmax 0.0336%, mid) (gnomAD).

What do computational predictors say about ADAM15 p.Arg796Pro (c.2387G>C)?

AlphaMissense predicts likely benign (score 0.3285) — an in-silico prediction, not a clinical call.

ADAM15 p.Arg796Pro

c.2387G>C · VCV3827808

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3285 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0336%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3285	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -11.84	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.20	donor loss, 22 bp away · masked 0 · deltas
Pangolin	Δ0.30	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.6	GERP 0.23, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 11 kb · p 2.7e-06 · regional, not allelic
Overall
CADD	23.8	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

Grpmax group 0.0336% Middle Eastern · 2/5,946 alleles

Filtering AF 0.0157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.013%

Overall 0.00158% 25/1,582,264 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0336%	2,973
African / African-American	0.0244%	4,095
Remaining individualsnot grpmax-eligible	0.00492%	20,319
European (non-Finnish)	0.000172%	580,777

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: ADAM15
Protein: p.Arg796Pro
Coding: c.2387G>C
MANE Select: NM_207197
Type: single nucleotide variant
Location: chr1:155061938 (GRCh38)
Gene constraint: LOEUF 0.826 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.35
Residue 796: the 'disordered' region

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

Similar variants

ADAM15 p.Arg796His Uncertain significance ★ ⚠ same residue
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

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-arg796pro (accessed [today's date]).

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