Is CD27 p.Cys232Trp (c.696T>G) pathogenic?

CD27 p.Cys232Trp (c.696T>G) is classified Uncertain significance in CD27 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-12). AlphaMissense: likely benign (0.1943); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CD27 p.Cys232Trp (c.696T>G)?

CD27 p.Cys232Trp (c.696T>G) is associated with Inborn genetic diseases, lymphoproliferative syndrome 2 (ClinVar).

How common is CD27 p.Cys232Trp (c.696T>G) in the general population?

CD27 p.Cys232Trp (c.696T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD27 p.Cys232Trp (c.696T>G)?

AlphaMissense predicts likely benign (score 0.1943) — an in-silico prediction, not a clinical call.

CD27 p.Cys232Trp

c.696T>G · rs1949541770 · VCV2126051

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1943 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1943	likely benign
REVEL	0.413	indeterminate
SaProt	LLR -7.25	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.21	acceptor loss, 9 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.51	GERP -1.9
Regional constraint	o/e 0.90	unconstrained · MANE · 6,293 bp · p 0.069 · regional, not allelic
Overall
CADD	20.8	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: CD27
Protein: p.Cys232Trp
Coding: c.696T>G
MANE Select: NM_001242
dbSNP: rs1949541770
Type: single nucleotide variant
Location: chr12:6451305 (GRCh38)
Gene constraint: LOEUF 0.946 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.79 · 5 PDB
Residue 232: the 'disordered' region

Full CD27 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

Also linked: lymphoproliferative syndrome 2

Similar variants

CD27 p.Cys53Tyr Pathogenic ★★ same condition
CD27 p.Ala164Pro Uncertain significance ★★ ⚠ same condition
CD27 p.Ala229Thr Uncertain significance ★★ ⚠ same condition
CD27 p.Arg155Thr Uncertain significance ★★ ⚠ same condition
CD27 p.Arg172Gln Uncertain significance ★★ ⚠ same condition
CD27 p.Arg172Gly Uncertain significance ★★ ⚠ same condition
CD27 p.Arg182Ser Uncertain significance ★★ ⚠ same condition
CD27 p.Arg238Lys 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/cd27-p-cys232trp (accessed [today's date]).

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