Is CD84 p.Pro72Leu (c.215C>T) pathogenic?

CD84 p.Pro72Leu (c.215C>T) is classified Uncertain significance in CD84 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-13). AlphaMissense: likely benign (0.2268); Rare (popmax 0.357%, afr).

How common is CD84 p.Pro72Leu (c.215C>T) in the general population?

CD84 p.Pro72Leu (c.215C>T) is rare (popmax 0.357%, afr) (gnomAD).

What do computational predictors say about CD84 p.Pro72Leu (c.215C>T)?

AlphaMissense predicts likely benign (score 0.2268) — an in-silico prediction, not a clinical call.

CD84 p.Pro72Leu

c.215C>T · rs143910468 · VCV2214446

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2268 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.357%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2268	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	LLR -11.35	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.86	GERP 1.3
Regional constraint	o/e 1.01	unconstrained · MANE · 31 kb · p 0.91 · regional, not allelic
Overall
CADD	17.42	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 0.357% African / African-American · 268/75,022 alleles

Filtering AF 0.322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.308%

Overall 0.0224% 362/1,613,960 alleles · rare exomes 195/1,461,722 · genomes 167/152,238 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.357%	280
Middle Eastern	0.0826%	1,211
Admixed American	0.0433%	2,307
Remaining individualsnot grpmax-eligible	0.0384%	2,604
South Asian	0.0296%	3,373
European (non-Finnish)	0.00102%	98,326

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.Pro72Leu
Coding: c.215C>T
MANE Select: NM_003874
dbSNP: rs143910468
Type: single nucleotide variant
Location: chr1:160565577 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.72 · 1 PDB
Residue 72: 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-pro72leu (accessed [today's date]).

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