Is CDR2L p.Trp18Arg (c.52T>C) pathogenic?

CDR2L p.Trp18Arg (c.52T>C) is classified Uncertain significance in CDR2L (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely pathogenic (0.9035); Ultra-rare (popmax 0.0392%, eas).

How common is CDR2L p.Trp18Arg (c.52T>C) in the general population?

CDR2L p.Trp18Arg (c.52T>C) is ultra-rare (popmax 0.0392%, eas) (gnomAD).

What do computational predictors say about CDR2L p.Trp18Arg (c.52T>C)?

AlphaMissense predicts likely pathogenic (score 0.9035) — an in-silico prediction, not a clinical call.

CDR2L p.Trp18Arg

c.52T>C · rs1418056942 · VCV2223290

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9035 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0392%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9035	likely pathogenic · top 9% in CDR2L
REVEL	0.574	indeterminate
SaProt	LLR -7.37	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.037 · regional, not allelic
Overall
CADD	26.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0392% East Asian · 15/38,226 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0196%

Overall 0.0013% 20/1,533,516 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0392%	2,548
Finnishnot grpmax-eligible	0.00171%	58,592
European (non-Finnish)	0.000351%	285,277

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: CDR2L
Protein: p.Trp18Arg
Coding: c.52T>C
MANE Select: NM_014603
dbSNP: rs1418056942
Type: single nucleotide variant
Location: chr17:74988095 (GRCh38)
Gene constraint: LOEUF 1.601 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.27

Full CDR2L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDR2L p.Ala201Glu Uncertain significance ★ ⚠ same type
CDR2L p.Ala222Thr Uncertain significance ★ ⚠ same type
CDR2L p.Ala274Asp Uncertain significance ★ ⚠ same type
CDR2L p.Ala5Ser Uncertain significance ★ ⚠ same type
CDR2L p.Ala81Ser Uncertain significance ★ ⚠ same type
CDR2L p.Arg121His Uncertain significance ★ ⚠ same type
CDR2L p.Arg146Gln Uncertain significance ★ ⚠ same type
CDR2L p.Arg146Trp 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/cdr2l-p-trp18arg (accessed [today's date]).

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