Is CD40 p.Phe129Cys (c.386T>G) pathogenic?

CD40 p.Phe129Cys (c.386T>G) is classified Uncertain significance in CD40 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-20). AlphaMissense: ambiguous (0.5487); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CD40 p.Phe129Cys (c.386T>G)?

CD40 p.Phe129Cys (c.386T>G) is associated with Inborn genetic diseases (ClinVar).

How common is CD40 p.Phe129Cys (c.386T>G) in the general population?

CD40 p.Phe129Cys (c.386T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD40 p.Phe129Cys (c.386T>G)?

AlphaMissense predicts ambiguous (score 0.5487) — an in-silico prediction, not a clinical call.

CD40 p.Phe129Cys

c.386T>G · rs2515709986 · VCV2476996

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5487 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5487	ambiguous
REVEL	0.457	indeterminate
SaProt	LLR -8.84	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -0.59, phastCons 0.12
Regional constraint	o/e 0.74	unconstrained · MANE · 11 kb · p 2e-06 · regional, not allelic
Overall
CADD	21.8	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

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: CD40
Protein: p.Phe129Cys
Coding: c.386T>G
MANE Select: NM_001250
dbSNP: rs2515709986
Type: single nucleotide variant
Location: chr20:46122739 (GRCh38)
Gene constraint: LOEUF 0.677 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 81.10 · 14 PDB
Residue 129: a disulfide bond; a β-strand

Full CD40 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD40 p.Ala25Ser Uncertain significance ★★ ⚠ same condition
CD40 p.Ile204Val Uncertain significance ★★ ⚠ same condition
CD40 p.Pro260Ser Uncertain significance ★★ ⚠ same condition
CD40 p.Ser245Cys Uncertain significance ★★ ⚠ same condition
CD40 p.Ser245Phe Uncertain significance ★★ ⚠ same condition
CD40 p.Thr112Lys Uncertain significance ★★ ⚠ same condition
CD40 p.Thr112Met Uncertain significance ★★ ⚠ same condition
CD40 p.Val138Ala Uncertain significance ★★ ⚠ same condition

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/cd40-p-phe129cys (accessed [today's date]).

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