Is ADAM9 p.Arg15= (c.45G>T) pathogenic?

ADAM9 p.Arg15= (c.45G>T) is classified Likely benign in ADAM9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-26). Very rare (popmax 0.00407%, nfe).

How common is ADAM9 p.Arg15= (c.45G>T) in the general population?

ADAM9 p.Arg15= (c.45G>T) is very rare (popmax 0.00407%, nfe) (gnomAD).

ADAM9 p.Arg15=

c.45G>T · rs758941052 · VCV1160569

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00407%, nfe)

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 4.5	GERP 0.81, phastCons 1
Overall
CADD	10.9	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00407% European (non-Finnish) · 48/1,179,610 alleles

Filtering AF 0.00315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.00336% 54/1,605,982 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00407%	24,575
South Asian	0.00329%	30,355
Remaining individualsnot grpmax-eligible	0.00321%	31,199
Admixed American	0.00167%	59,988

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: ADAM9
Protein: p.Arg15=
Coding: c.45G>T
MANE Select: NM_003816
dbSNP: rs758941052
Type: single nucleotide variant
Location: chr8:38997108 (GRCh38)
Gene constraint: LOEUF 0.575 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.14

Full ADAM9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ADAM9 p.Arg15Gly Uncertain significance ★ ⚠ same residue
ADAM9 p.Arg15Pro Uncertain significance ★ ⚠ same residue
ADAM9 p.Tyr213Ter Pathogenic/Likely pathogenic ★★ same type
ADAM9 c.195+5G>A Uncertain significance ★★ same type
ADAM9 c.997-3C>G Uncertain significance ★★ same type
ADAM9 p.Ala145Glu Uncertain significance ★★ ⚠ same type
ADAM9 p.Ala424Thr Uncertain significance ★★ ⚠ same type
ADAM9 p.Ala510Thr 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/adam9-p-arg15 (accessed [today's date]).

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