Is CD27 p.Ser149Arg (c.445A>C) pathogenic?

CD27 p.Ser149Arg (c.445A>C) is classified Uncertain significance in CD27 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-10). AlphaMissense: likely benign (0.1782); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CD27 p.Ser149Arg (c.445A>C)?

CD27 p.Ser149Arg (c.445A>C) is associated with Inborn genetic diseases (ClinVar).

How common is CD27 p.Ser149Arg (c.445A>C) in the general population?

CD27 p.Ser149Arg (c.445A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD27 p.Ser149Arg (c.445A>C)?

AlphaMissense predicts likely benign (score 0.1782) — an in-silico prediction, not a clinical call.

CD27 p.Ser149Arg

c.445A>C · VCV3829474

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1782 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1782	likely benign
REVEL	0.177	moderately benign-leaning
SaProt	LLR -6.90	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 -0.29	GERP -2
Regional constraint	o/e 0.90	unconstrained · MANE · 6,293 bp · p 0.069 · regional, not allelic
Overall
CADD	1.243	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.Ser149Arg
Coding: c.445A>C
MANE Select: NM_001242
Type: single nucleotide variant
Location: chr12:6450349 (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

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

Similar variants

CD27 p.Ala164Pro Uncertain significance ★★ ⚠ same condition
CD27 p.Arg3Gln Uncertain significance ★★ ⚠ same condition
CD27 p.Arg85Gln Uncertain significance ★★ ⚠ same condition
CD27 p.Cys232Trp Uncertain significance ★★ ⚠ same condition
CD27 p.Glu255Gln Uncertain significance ★★ ⚠ same condition
CD27 p.Gly13Trp Uncertain significance ★★ same condition
CD27 p.His139Gln Uncertain significance ★★ ⚠ same condition
CD27 p.Leu163Pro 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-ser149arg (accessed [today's date]).

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