Is CD84 p.Ile111Leu (c.331A>T) pathogenic?

CD84 p.Ile111Leu (c.331A>T) is classified Uncertain significance in CD84 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-30). AlphaMissense: ambiguous (0.3749); Ultra-rare (popmax 0.0141%, nfe).

How common is CD84 p.Ile111Leu (c.331A>T) in the general population?

CD84 p.Ile111Leu (c.331A>T) is ultra-rare (popmax 0.0141%, nfe) (gnomAD).

What do computational predictors say about CD84 p.Ile111Leu (c.331A>T)?

AlphaMissense predicts ambiguous (score 0.3749) — an in-silico prediction, not a clinical call.

CD84 p.Ile111Leu

c.331A>T · rs370980795 · VCV2598384

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3749 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0141%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3749	ambiguous
REVEL	0.297	indeterminate
SaProt	LLR -10.01	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.58	GERP 2.2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 31 kb · p 0.91 · regional, not allelic
Overall
CADD	22.0	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 0.0141% European (non-Finnish) · 166/1,179,884 alleles

Filtering AF 0.0123% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0116%

Overall 0.0108% 175/1,613,830 alleles · ultra-rare exomes 166/1,461,644 · genomes 9/152,186 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0141%	7,108
Admixed American	0.0117%	8,569
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,588
African / African-American	0.00134%	74,904

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.Ile111Leu
Coding: c.331A>T
MANE Select: NM_003874
dbSNP: rs370980795
Type: single nucleotide variant
Location: chr1:160565461 (GRCh38)
Gene constraint: LOEUF 0.91 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.72 · 1 PDB
Residue 111: a β-strand; 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-ile111leu (accessed [today's date]).

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