Is CD84 p.Pro198Ala (c.592C>G) pathogenic?

CD84 p.Pro198Ala (c.592C>G) is classified Uncertain significance in CD84 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-08). AlphaMissense: likely benign (0.2454); Rare (popmax 0.144%, sas).

How common is CD84 p.Pro198Ala (c.592C>G) in the general population?

CD84 p.Pro198Ala (c.592C>G) is rare (popmax 0.144%, sas) (gnomAD).

What do computational predictors say about CD84 p.Pro198Ala (c.592C>G)?

AlphaMissense predicts likely benign (score 0.2454) — an in-silico prediction, not a clinical call.

CD84 p.Pro198Ala

c.592C>G · VCV4650723

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2454 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.144%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2454	likely benign
REVEL	0.182	moderately benign-leaning
SaProt	LLR -9.87	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 8.2	GERP 2.2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 31 kb · p 0.91 · regional, not allelic
Overall
CADD	25.3	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 0.144% South Asian · 131/91,084 alleles

Filtering AF 0.124% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.116%

Overall 0.00917% 148/1,614,202 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.144%	695
Middle Eastern	0.033%	3,030
Remaining individualsnot grpmax-eligible	0.0064%	15,626
East Asian	0.00223%	44,882
African / African-American	0.00133%	75,048
European (non-Finnish)	0.000763%	131,115

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.Pro198Ala
Coding: c.592C>G
MANE Select: NM_003874
Type: single nucleotide variant
Location: chr1:160553943 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.72 · 1 PDB
Residue 198: 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-pro198ala (accessed [today's date]).

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