Is CD84 p.Pro184Ala (c.550C>G) pathogenic?

CD84 p.Pro184Ala (c.550C>G) is classified Uncertain significance in CD84 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-09). AlphaMissense: likely benign (0.0762); Very rare (popmax 0.00133%, afr).

How common is CD84 p.Pro184Ala (c.550C>G) in the general population?

CD84 p.Pro184Ala (c.550C>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CD84 p.Pro184Ala (c.550C>G)?

AlphaMissense predicts likely benign (score 0.0762) — an in-silico prediction, not a clinical call.

CD84 p.Pro184Ala

c.550C>G · rs1185131252 · VCV2242046

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0762 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0762	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -7.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.3, phastCons 0.7
Regional constraint	o/e 1.01	unconstrained · MANE · 31 kb · p 0.91 · regional, not allelic
Overall
CADD	17.2	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 0.00133% African / African-American · 1/74,930 alleles

Overall 0.000657% 1/152,194 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
Protein: p.Pro184Ala
Coding: c.550C>G
MANE Select: NM_003874
dbSNP: rs1185131252
Type: single nucleotide variant
Location: chr1:160553985 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.72 · 1 PDB
Residue 184: a disulfide bond; the ig-like c2-type domain

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

Similar variants

CD84 c.760+12C>T Uncertain significance ★ ⚠ same type
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

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-p-pro184ala (accessed [today's date]).

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