Is CDR2 p.Val413Met (c.1237G>A) pathogenic?

CDR2 p.Val413Met (c.1237G>A) is classified Uncertain significance in CDR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-07). AlphaMissense: likely benign (0.0875); Ultra-rare (popmax 0.0164%, mid).

How common is CDR2 p.Val413Met (c.1237G>A) in the general population?

CDR2 p.Val413Met (c.1237G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CDR2 p.Val413Met (c.1237G>A)?

AlphaMissense predicts likely benign (score 0.0875) — an in-silico prediction, not a clinical call.

CDR2 p.Val413Met

c.1237G>A · rs745588256 · VCV2355258

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0875 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0875	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -8.26	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 -10
Regional constraint	o/e 0.91	unconstrained · MANE · 27 kb · p 0.028 · regional, not allelic
Overall
CADD	0.001	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00142% 23/1,614,074 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
East Asian	0.00223%	44,896
South Asian	0.0022%	45,544
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	0.00144%	69,414
African / African-American	0.00133%	74,938

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: CDR2
Protein: p.Val413Met
Coding: c.1237G>A
MANE Select: NM_001802
dbSNP: rs745588256
Type: single nucleotide variant
Location: chr16:22347093 (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.Val413Leu 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-val413met (accessed [today's date]).

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