Is CDR2L p.Gly310Asp (c.929G>A) pathogenic?

CDR2L p.Gly310Asp (c.929G>A) is classified Uncertain significance in CDR2L (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-07). AlphaMissense: likely benign (0.1099); Very rare (popmax 0.000267%, nfe).

How common is CDR2L p.Gly310Asp (c.929G>A) in the general population?

CDR2L p.Gly310Asp (c.929G>A) is very rare (popmax 0.000267%, nfe) (gnomAD).

What do computational predictors say about CDR2L p.Gly310Asp (c.929G>A)?

AlphaMissense predicts likely benign (score 0.1099) — an in-silico prediction, not a clinical call.

CDR2L p.Gly310Asp

c.929G>A · VCV3489749

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1099 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000267%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1099	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -7.24	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 6.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 16 kb · p 0.037 · regional, not allelic
Overall
CADD	18.44	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 0.000267% European (non-Finnish) · 3/1,121,622 alleles

Filtering AF 7.1e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.000201% 3/1,492,052 alleles · very rare

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.Gly310Asp
Coding: c.929G>A
MANE Select: NM_014603
Type: single nucleotide variant
Location: chr17:75003605 (GRCh38)
Gene constraint: LOEUF 1.601 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.27
Residue 310: the 'disordered' region

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

Similar variants

CDR2L p.Gly310Cys 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-gly310asp (accessed [today's date]).

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