Is ADAM9 p.Pro792Ala (c.2374C>G) pathogenic?

ADAM9 p.Pro792Ala (c.2374C>G) is classified Uncertain significance in ADAM9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-05). AlphaMissense: likely benign (0.0727); Very rare (popmax 0.000763%, nfe).

How common is ADAM9 p.Pro792Ala (c.2374C>G) in the general population?

ADAM9 p.Pro792Ala (c.2374C>G) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about ADAM9 p.Pro792Ala (c.2374C>G)?

AlphaMissense predicts likely benign (score 0.0727) — an in-silico prediction, not a clinical call.

ADAM9 p.Pro792Ala

c.2374C>G · rs1295134926 · VCV1432489

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0727 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0727	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -8.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 26 kb · p 0.88 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000763% European (non-Finnish) · 9/1,179,974 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000616% 9/1,461,820 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: ADAM9
Protein: p.Pro792Ala
Coding: c.2374C>G
MANE Select: NM_003816
dbSNP: rs1295134926
Type: single nucleotide variant
Location: chr8:39103614 (GRCh38)
Gene constraint: LOEUF 0.575 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.14
Residue 792: the 'disordered' region

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

Similar variants

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
ADAM9 p.Ala534Pro Uncertain significance ★★ ⚠ same type
ADAM9 p.Arg117Trp 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-pro792ala (accessed [today's date]).

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