Is ADAM9 p.Ala367Val (c.1100C>T) pathogenic?

ADAM9 p.Ala367Val (c.1100C>T) is classified Uncertain significance in ADAM9 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-04). AlphaMissense: likely benign (0.0996); Very rare (popmax 6.84e-05%).

How common is ADAM9 p.Ala367Val (c.1100C>T) in the general population?

ADAM9 p.Ala367Val (c.1100C>T) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about ADAM9 p.Ala367Val (c.1100C>T)?

AlphaMissense predicts likely benign (score 0.0996) — an in-silico prediction, not a clinical call.

ADAM9 p.Ala367Val

c.1100C>T · rs781504873 · VCV1008688

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0996 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0996	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -4.25	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 4.1	GERP 1, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 60 kb · p 8.2e-12 · regional, not allelic
Overall
CADD	16.12	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 6.84e-05%

Overall 6.84e-05% 1/1,461,846 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.Ala367Val
Coding: c.1100C>T
MANE Select: NM_003816
dbSNP: rs781504873
Type: single nucleotide variant
Location: chr8:39026780 (GRCh38)
Gene constraint: LOEUF 0.575 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.14
Residue 367: a disulfide bond; the peptidase m12b domain

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

Similar variants

ADAM9 p.Ala367= Likely benign ★★ 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
ADAM9 p.Ala534Pro 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-ala367val (accessed [today's date]).

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