Is CD27 p.Val50Met (c.148G>A) pathogenic?

CD27 p.Val50Met (c.148G>A) is classified Uncertain significance in CD27 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-21). AlphaMissense: likely benign (0.1919); Ultra-rare (popmax 0.0253%, sas); Associated with Inborn genetic diseases.

What condition is associated with CD27 p.Val50Met (c.148G>A)?

CD27 p.Val50Met (c.148G>A) is associated with Inborn genetic diseases, lymphoproliferative syndrome 2 (ClinVar).

How common is CD27 p.Val50Met (c.148G>A) in the general population?

CD27 p.Val50Met (c.148G>A) is ultra-rare (popmax 0.0253%, sas) (gnomAD).

What do computational predictors say about CD27 p.Val50Met (c.148G>A)?

AlphaMissense predicts likely benign (score 0.1919) — an in-silico prediction, not a clinical call.

CD27 p.Val50Met

c.148G>A · rs763617266 · VCV1022183

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1919 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1919	likely benign
REVEL	0.364	indeterminate
SaProt	LLR -7.06	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 3.3	GERP -1.2, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 6,293 bp · p 0.069 · regional, not allelic
Overall
CADD	22.3	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 0.0253% South Asian · 23/91,080 alleles

Filtering AF 0.0172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0146%

Overall 0.0041% 60/1,461,862 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0253%	3,960
Remaining individualsnot grpmax-eligible	0.0144%	6,946
Admixed American	0.00666%	15,006
East Asian	0.00223%	44,890
European (non-Finnish)	0.00195%	51,305

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.Val50Met
Coding: c.148G>A
MANE Select: NM_001242
dbSNP: rs763617266
Type: single nucleotide variant
Location: chr12:6445435 (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 50: a disulfide bond; a β-strand

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-val50met (accessed [today's date]).

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