Is CD83 p.Pro89Ser (c.265C>T) pathogenic?

CD83 p.Pro89Ser (c.265C>T) is classified Uncertain significance in CD83 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-07). AlphaMissense: likely benign (0.1049); Absent from gnomAD v4.1.

How common is CD83 p.Pro89Ser (c.265C>T) in the general population?

CD83 p.Pro89Ser (c.265C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD83 p.Pro89Ser (c.265C>T)?

AlphaMissense predicts likely benign (score 0.1049) — an in-silico prediction, not a clinical call.

CD83 p.Pro89Ser

c.265C>T · VCV4223052

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1049 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1049	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.84	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 0.15	GERP -1.8
Regional constraint	o/e 1.00	unconstrained · MANE · 17 kb · p 0.99 · regional, not allelic
Overall
CADD	2.111	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD83
Protein: p.Pro89Ser
Coding: c.265C>T
MANE Select: NM_004233
Type: single nucleotide variant
Location: chr6:14131631 (GRCh38)
Gene constraint: LOEUF 1.383 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.45 · 4 PDB
Residue 89: 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.Ala143Val Uncertain significance ★ ⚠ same type
CD83 p.Ala84Ser Uncertain significance ★ ⚠ same type
CD83 p.Ala84Thr 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

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-pro89ser (accessed [today's date]).

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