Is CDR2 p.Pro17Gln (c.50C>A) pathogenic?

CDR2 p.Pro17Gln (c.50C>A) is classified Uncertain significance in CDR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.2671); Absent from gnomAD v4.1.

How common is CDR2 p.Pro17Gln (c.50C>A) in the general population?

CDR2 p.Pro17Gln (c.50C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDR2 p.Pro17Gln (c.50C>A)?

AlphaMissense predicts likely benign (score 0.2671) — an in-silico prediction, not a clinical call.

CDR2 p.Pro17Gln

c.50C>A · VCV4651653

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2671 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,603,656)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2671	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -8.32	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 5.3	phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 27 kb · p 0.028 · regional, not allelic
Overall
CADD	24.7	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

No allele count reported in gnomAD v4.1 (AN 1,603,656). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDR2
Protein: p.Pro17Gln
Coding: c.50C>A
MANE Select: NM_001802
Type: single nucleotide variant
Location: chr16:22374260 (GRCh38)
Gene constraint: LOEUF 0.879 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.84

Full CDR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDR2 p.Pro17Ser Uncertain significance ★ ⚠ same residue
CDR2 p.Ala107Val Uncertain significance ★ ⚠ same type
CDR2 p.Ala155Thr Uncertain significance ★ ⚠ same type
CDR2 p.Ala178Thr Uncertain significance ★ ⚠ same type
CDR2 p.Ala252Pro Uncertain significance ★ ⚠ same type
CDR2 p.Ala319Ser Uncertain significance ★ ⚠ same type
CDR2 p.Ala355Thr Uncertain significance ★ ⚠ same type
CDR2 p.Ala394Thr Uncertain significance ★ ⚠ same type

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/cdr2-p-pro17gln (accessed [today's date]).

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