Is CD83 p.Val122Leu (c.364G>T) pathogenic?

CD83 p.Val122Leu (c.364G>T) is classified Uncertain significance in CD83 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: ambiguous (0.4117); Very rare (popmax 0.00746%, nfe).

How common is CD83 p.Val122Leu (c.364G>T) in the general population?

CD83 p.Val122Leu (c.364G>T) is very rare (popmax 0.00746%, nfe) (gnomAD).

What do computational predictors say about CD83 p.Val122Leu (c.364G>T)?

AlphaMissense predicts ambiguous (score 0.4117) — an in-silico prediction, not a clinical call.

CD83 p.Val122Leu

c.364G>T · rs973193584 · VCV3140686

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4117 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00746%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4117	ambiguous
REVEL	0.233	benign-leaning
SaProt	LLR -10.22	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.4	GERP 1.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 17 kb · p 0.99 · regional, not allelic
Overall
CADD	24.2	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 0.00746% European (non-Finnish) · 88/1,179,298 alleles

Filtering AF 0.00615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00573%

Overall 0.00545% 88/1,613,238 alleles · very rare

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.Val122Leu
Coding: c.364G>T
MANE Select: NM_004233
dbSNP: rs973193584
Type: single nucleotide variant
Location: chr6:14131730 (GRCh38)
Gene constraint: LOEUF 1.383 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.45 · 4 PDB
Residue 122: a β-strand

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-val122leu (accessed [today's date]).

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