Is CD83 p.Ala84Thr (c.250G>A) pathogenic?

CD83 p.Ala84Thr (c.250G>A) is classified Uncertain significance in CD83 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-13). AlphaMissense: likely benign (0.0689); Ultra-rare (popmax 0.0164%, mid).

How common is CD83 p.Ala84Thr (c.250G>A) in the general population?

CD83 p.Ala84Thr (c.250G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CD83 p.Ala84Thr (c.250G>A)?

AlphaMissense predicts likely benign (score 0.0689) — an in-silico prediction, not a clinical call.

CD83 p.Ala84Thr

c.250G>A · VCV4223050

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0689 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0689	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -5.74	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 1.2	GERP -2.7
Regional constraint	o/e 1.00	unconstrained · MANE · 17 kb · p 0.99 · regional, not allelic
Overall
CADD	13.81	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00579%

Overall 0.0018% 29/1,613,936 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Admixed American	0.015%	6,666
Remaining individualsnot grpmax-eligible	0.0048%	20,829
East Asian	0.00446%	22,446
African / African-American	0.00134%	74,868
European (non-Finnish)	0.0011%	90,769

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: CD83
Protein: p.Ala84Thr
Coding: c.250G>A
MANE Select: NM_004233
Type: single nucleotide variant
Location: chr6:14131616 (GRCh38)
Gene constraint: LOEUF 1.383 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.45 · 4 PDB
Residue 84: a disulfide bond; the ig-like v-type domain

Full CD83 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD83 p.Ala84Ser Uncertain significance ★ ⚠ same residue
CD83 p.Ala143Val Uncertain significance ★ ⚠ same type
CD83 p.Arg167Gln Uncertain significance ★ ⚠ same type
CD83 p.Asn191Asp Uncertain significance ★ ⚠ same type
CD83 p.Asn79His Uncertain significance ★ ⚠ same type
CD83 p.Asn79Ile Uncertain significance ★ ⚠ same type
CD83 p.Asp30Asn Uncertain significance ★ ⚠ same type
CD83 p.Asp40Tyr 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/cd83-p-ala84thr (accessed [today's date]).

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