Is ADAM9 p.Tyr511Ser (c.1532A>C) pathogenic?

ADAM9 p.Tyr511Ser (c.1532A>C) is classified Uncertain significance in ADAM9 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-09-04). AlphaMissense: ambiguous (0.3839); Absent from gnomAD v4.1.

How common is ADAM9 p.Tyr511Ser (c.1532A>C) in the general population?

ADAM9 p.Tyr511Ser (c.1532A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADAM9 p.Tyr511Ser (c.1532A>C)?

AlphaMissense predicts ambiguous (score 0.3839) — an in-silico prediction, not a clinical call.

ADAM9 p.Tyr511Ser

c.1532A>C · rs560445503 · VCV1041051

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3839 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3839	ambiguous
REVEL	0.628	indeterminate
SaProt	LLR -11.25	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 60 kb · p 8.2e-12 · regional, not allelic
Overall
CADD	27.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ADAM9
Protein: p.Tyr511Ser
Coding: c.1532A>C
MANE Select: NM_003816
dbSNP: rs560445503
Type: single nucleotide variant
Location: chr8:39055713 (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.Tyr511Cys 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
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-tyr511ser (accessed [today's date]).

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