Is CD27 p.His80fs (c.239dup) pathogenic?

CD27 p.His80fs (c.239dup) is classified Pathogenic/Likely pathogenic in CD27 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-05). Very rare (popmax 0.00144%, nfe); Associated with CD27-related disorder.

What condition is associated with CD27 p.His80fs (c.239dup)?

CD27 p.His80fs (c.239dup) is associated with CD27-related disorder, lymphoproliferative syndrome 2 (ClinVar).

How common is CD27 p.His80fs (c.239dup) in the general population?

CD27 p.His80fs (c.239dup) is very rare (popmax 0.00144%, nfe) (gnomAD).

CD27 p.His80fs

c.239dup · rs748418658 · VCV578414

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Conditions

CD27-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.5	GERP 1.3, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00144% European (non-Finnish) · 17/1,180,022 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00112% 18/1,613,804 alleles · very rare exomes 16/1,461,622 · genomes 2/152,182 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00144%	69,413
African / African-American	0.00133%	74,926

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: CD27
Protein: p.His80fs
Coding: c.239dup
MANE Select: NM_001242
dbSNP: rs748418658
Type: Duplication
Location: chr12:6445525 (GRCh38)
Gene constraint: LOEUF 0.946 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 71.79 · 5 PDB

Full CD27 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CD27-related disorder

Also linked: lymphoproliferative syndrome 2

Similar variants

CD27 c.136+11dup Benign ★ same condition
CD27 p.Asp52fs Pathogenic/Likely pathogenic ★★ same condition
CD27 p.Cys53Tyr Pathogenic ★★ same condition
CD27 p.Leu136fs Pathogenic/Likely 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

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-his80fs (accessed [today's date]).

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