Is CD27 p.Ser186Gly (c.556A>G) pathogenic?

CD27 p.Ser186Gly (c.556A>G) is classified Uncertain significance in CD27 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). AlphaMissense: likely benign (0.0996); Very rare (popmax 0.01%, amr); Associated with Inborn genetic diseases.

What condition is associated with CD27 p.Ser186Gly (c.556A>G)?

CD27 p.Ser186Gly (c.556A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CD27 p.Ser186Gly (c.556A>G) in the general population?

CD27 p.Ser186Gly (c.556A>G) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about CD27 p.Ser186Gly (c.556A>G)?

AlphaMissense predicts likely benign (score 0.0996) — an in-silico prediction, not a clinical call.

CD27 p.Ser186Gly

c.556A>G · VCV3829473

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0996 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0996	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -7.78	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 0.99, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 6,293 bp · p 0.069 · regional, not allelic
Overall
CADD	21.4	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

Grpmax group 0.01% Admixed American · 6/60,028 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.00041% 6/1,461,872 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: CD27
Protein: p.Ser186Gly
Coding: c.556A>G
MANE Select: NM_001242
Type: single nucleotide variant
Location: chr12:6450912 (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

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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-ser186gly (accessed [today's date]).

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