Is CDR2L p.Leu176Gln (c.527T>A) pathogenic?

CDR2L p.Leu176Gln (c.527T>A) is classified Uncertain significance in CDR2L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-24). AlphaMissense: likely benign (0.0958); Absent from gnomAD v4.1.

How common is CDR2L p.Leu176Gln (c.527T>A) in the general population?

CDR2L p.Leu176Gln (c.527T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDR2L p.Leu176Gln (c.527T>A)?

AlphaMissense predicts likely benign (score 0.0958) — an in-silico prediction, not a clinical call.

CDR2L p.Leu176Gln

c.527T>A · VCV3265604

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0958 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,565,626)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0958	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -6.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.1	GERP 0.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.037 · regional, not allelic
Overall
CADD	19.21	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 1,565,626). 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: CDR2L
Protein: p.Leu176Gln
Coding: c.527T>A
MANE Select: NM_014603
Type: single nucleotide variant
Location: chr17:75003203 (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-leu176gln (accessed [today's date]).

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