Is ADAM9 p.Asp697= (c.2091C>T) pathogenic?

ADAM9 p.Asp697= (c.2091C>T) is classified Conflicting classifications of pathogenicity in ADAM9 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0734%, nfe); Associated with cone-rod dystrophy 9.

What condition is associated with ADAM9 p.Asp697= (c.2091C>T)?

ADAM9 p.Asp697= (c.2091C>T) is associated with cone-rod dystrophy 9 (ClinVar).

How common is ADAM9 p.Asp697= (c.2091C>T) in the general population?

ADAM9 p.Asp697= (c.2091C>T) is ultra-rare (popmax 0.0734%, nfe) (gnomAD).

How is Cone rod dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ADAM9 p.Asp697=

c.2091C>T · rs138938731 · VCV729582

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0734%, nfe)

Conditions

cone-rod dystrophy 9

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 -8.5	GERP -4.8
Overall
CADD	2.233	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0734% European (non-Finnish) · 866/1,179,886 alleles

Filtering AF 0.0693% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0677%

Overall 0.0568% 916/1,613,814 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0734%	1,362
Remaining individualsnot grpmax-eligible	0.04%	2,500
Middle Eastern	0.0165%	6,058
African / African-American	0.016%	6,249
Admixed American	0.015%	6,668
East Asian	0.00223%	44,816
South Asian	0.0022%	45,539

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.Asp697=
Coding: c.2091C>T
MANE Select: NM_003816
dbSNP: rs138938731
Type: single nucleotide variant
Location: chr8:39090069 (GRCh38)
Gene constraint: LOEUF 0.575 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.14
Residue 697: the egf-like domain

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

Disease context

cone-rod dystrophy 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Cone rod dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Adolescent, Adult, Childhood
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

ADAM9 p.Tyr213Ter Pathogenic/Likely pathogenic ★★ same condition
ADAM9 c.997-3C>G Uncertain significance ★★ same condition
ADAM9 p.Ala510Thr Uncertain significance ★★ ⚠ same condition
ADAM9 p.Asn501Asp Uncertain significance ★★ ⚠ same condition
ADAM9 p.Asp132Tyr Uncertain significance ★★ ⚠ same condition
ADAM9 p.Asp362Gly Uncertain significance ★★ ⚠ same condition
ADAM9 p.Leu695Trp Uncertain significance ★★ ⚠ same condition
ADAM9 p.Met516Val Uncertain significance ★★ ⚠ same condition

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-asp697 (accessed [today's date]).

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