Is CDR2L p.Arg428Trp (c.1282C>T) pathogenic?

CDR2L p.Arg428Trp (c.1282C>T) is classified Uncertain significance in CDR2L (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: ambiguous (0.4132); Ultra-rare (popmax 0.0674%, nfe).

How common is CDR2L p.Arg428Trp (c.1282C>T) in the general population?

CDR2L p.Arg428Trp (c.1282C>T) is ultra-rare (popmax 0.0674%, nfe) (gnomAD).

What do computational predictors say about CDR2L p.Arg428Trp (c.1282C>T)?

AlphaMissense predicts ambiguous (score 0.4132) — an in-silico prediction, not a clinical call.

CDR2L p.Arg428Trp

c.1282C>T · rs144796205 · VCV2210221

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4132 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0674%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4132	ambiguous
REVEL	0.397	indeterminate
SaProt	LLR -9.05	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.78	GERP -0.5, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.037 · regional, not allelic
Overall
CADD	26.6	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 0.0674% European (non-Finnish) · 794/1,178,484 alleles

Filtering AF 0.0635% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0619%

Overall 0.0549% 884/1,610,360 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0674%	1,484
South Asian	0.0443%	2,259
Remaining individualsnot grpmax-eligible	0.0401%	2,495
Ashkenazi Jewishnot grpmax-eligible	0.0373%	2,683
African / African-American	0.0107%	9,375
Admixed American	0.0101%	9,923

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.Arg428Trp
Coding: c.1282C>T
MANE Select: NM_014603
dbSNP: rs144796205
Type: single nucleotide variant
Location: chr17:75003958 (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.Arg428Leu Uncertain significance ★ ⚠ same residue
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

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-arg428trp (accessed [today's date]).

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