Is CD84 p.Pro90Leu (c.269C>T) pathogenic?

CD84 p.Pro90Leu (c.269C>T) is classified Uncertain significance in CD84 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-12). AlphaMissense: likely benign (0.1218); Ultra-rare (popmax 0.0165%, mid).

How common is CD84 p.Pro90Leu (c.269C>T) in the general population?

CD84 p.Pro90Leu (c.269C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CD84 p.Pro90Leu (c.269C>T)?

AlphaMissense predicts likely benign (score 0.1218) — an in-silico prediction, not a clinical call.

CD84 p.Pro90Leu

c.269C>T · rs199818239 · VCV2363410

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1218 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1218	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -6.34	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 -0.001	GERP -1.6
Regional constraint	o/e 1.01	unconstrained · MANE · 31 kb · p 0.91 · regional, not allelic
Overall
CADD	3.893	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 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00956%

Overall 0.0096% 155/1,613,956 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
European (non-Finnish)	0.0118%	8,488
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,865
Admixed American	0.00833%	12,001
Remaining individualsnot grpmax-eligible	0.008%	12,500
African / African-American	0.00267%	37,517

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.Pro90Leu
Coding: c.269C>T
MANE Select: NM_003874
dbSNP: rs199818239
Type: single nucleotide variant
Location: chr1:160565523 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.72 · 1 PDB
Residue 90: a turn; the ig-like v-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-pro90leu (accessed [today's date]).

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