Is CD9 p.Met70Ile (c.210G>A) pathogenic?

CD9 p.Met70Ile (c.210G>A) is classified Uncertain significance in CD9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-29). AlphaMissense: likely pathogenic (0.9611); Very rare (popmax 0.00709%, amr).

How common is CD9 p.Met70Ile (c.210G>A) in the general population?

CD9 p.Met70Ile (c.210G>A) is very rare (popmax 0.00709%, amr) (gnomAD).

What do computational predictors say about CD9 p.Met70Ile (c.210G>A)?

AlphaMissense predicts likely pathogenic (score 0.9611) — an in-silico prediction, not a clinical call.

CD9 p.Met70Ile

c.210G>A · VCV4223077

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9611 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00709%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9611	likely pathogenic
REVEL	0.407	indeterminate
SaProt	LLR -9.95	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 37 kb · p 0.018 · regional, not allelic
Overall
CADD	22.0	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

Grpmax group 0.00709% Admixed American · 4/56,402 alleles

Filtering AF 0.00235% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00141%

Overall 0.000253% 4/1,581,612 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.Met70Ile
Coding: c.210G>A
MANE Select: NM_001769
Type: single nucleotide variant
Location: chr12:6232666 (GRCh38)
Gene constraint: LOEUF 0.555 · pLI 0.93 (gnomAD)
Structure: AlphaFold pLDDT 88.38 · 5 PDB
Residue 70: 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.Leu96Phe Uncertain significance ★ ⚠ same type
CD9 p.Lys186Glu Uncertain significance ★ ⚠ same type
CD9 p.Met227Leu 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-met70ile (accessed [today's date]).

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