Is CD84 c.760+12C>T pathogenic?

CD84 c.760+12C>T is classified Uncertain significance in CD84 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: likely benign (0.0757); Very rare (popmax 0.000169%, nfe).

How common is CD84 c.760+12C>T in the general population?

CD84 c.760+12C>T is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about CD84 c.760+12C>T?

AlphaMissense predicts likely benign (score 0.0757) — an in-silico prediction, not a clinical call.

CD84 c.760+12C>T

VCV4223061

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0757 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0757	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -5.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
Splice region	donor +12	near-intronic (+12 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.76	GERP -4, phastCons 0.17
Non-coding constraint	Z 1.84	1 kb window · o/e 0.87 · regional · uncalibrated
Overall
CADD	14.1	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 0.000169% European (non-Finnish) · 2/1,180,018 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,874 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: CD84
Coding: c.760+12C>T
MANE Select: NM_003874
Type: single nucleotide variant
Location: chr1:160553366 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.72 · 1 PDB

Full CD84 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD84 c.760+668A>G Uncertain significance ★ ⚠ same type
CD84 c.760+670C>G Uncertain significance ★ ⚠ same type
CD84 p.Ala216Thr Uncertain significance ★ ⚠ same type
CD84 p.Ala274Thr Uncertain significance ★ ⚠ same type
CD84 p.Ala71Thr Uncertain significance ★ ⚠ same type
CD84 p.Ala71Val Uncertain significance ★ ⚠ same type
CD84 p.Arg123Cys Uncertain significance ★ ⚠ same type
CD84 p.Arg131Gln 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/cd84-c-760-plus-12c-t (accessed [today's date]).

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