Is CD9 p.Leu96Phe (c.286C>T) pathogenic?

CD9 p.Leu96Phe (c.286C>T) is classified Uncertain significance in CD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: likely pathogenic (0.9915); Very rare (popmax 8.48e-05%, nfe).

How common is CD9 p.Leu96Phe (c.286C>T) in the general population?

CD9 p.Leu96Phe (c.286C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CD9 p.Leu96Phe (c.286C>T)?

AlphaMissense predicts likely pathogenic (score 0.9915) — an in-silico prediction, not a clinical call.

CD9 p.Leu96Phe

c.286C>T · rs2497507911 · VCV3140707

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9915 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9915	likely pathogenic
REVEL	0.65	pathogenic-leaning
SaProt	LLR -12.97	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 37 kb · p 0.018 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.48e-05% European (non-Finnish) · 1/1,179,890 alleles

Overall 6.84e-05% 1/1,461,734 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: CD9
Protein: p.Leu96Phe
Coding: c.286C>T
MANE Select: NM_001769
dbSNP: rs2497507911
Type: single nucleotide variant
Location: chr12:6233424 (GRCh38)
Gene constraint: LOEUF 0.555 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 88.38 · 5 PDB
Residue 96: an α-helix

Full CD9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD9 c.447+8G>A Benign ★★ same type
CD9 p.Asn51Thr Uncertain significance ★ ⚠ same type
CD9 p.Glu103Gln Uncertain significance ★ ⚠ same type
CD9 p.Gly210Ala Uncertain significance ★ ⚠ same type
CD9 p.Gly80Arg Uncertain significance ★ ⚠ same type
CD9 p.Lys186Glu Uncertain significance ★ ⚠ same type
CD9 p.Met227Leu Uncertain significance ★ ⚠ same type
CD9 p.Met70Ile 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/cd9-p-leu96phe (accessed [today's date]).

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