Is CBR3 p.Ser2Trp (c.5C>G) pathogenic?

CBR3 p.Ser2Trp (c.5C>G) is classified Uncertain significance in CBR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: likely benign (0.2143); Absent from gnomAD v4.1.

How common is CBR3 p.Ser2Trp (c.5C>G) in the general population?

CBR3 p.Ser2Trp (c.5C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CBR3 p.Ser2Trp (c.5C>G)?

AlphaMissense predicts likely benign (score 0.2143) — an in-silico prediction, not a clinical call.

CBR3 p.Ser2Trp

c.5C>G · rs770963323 · VCV3138034

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2143 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,481,564)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2143	likely benign
REVEL	0.395	indeterminate
SaProt	LLR -9.83	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 11 kb · p 0.0091 · regional, not allelic
Overall
CADD	27.8	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 1,481,564). 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: CBR3
Protein: p.Ser2Trp
Coding: c.5C>G
MANE Select: NM_001236
dbSNP: rs770963323
Type: single nucleotide variant
Location: chr21:36135197 (GRCh38)
Gene constraint: LOEUF 1.846 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.66 · 1 PDB
Residue 2: a modified residue (n-acetylserine)

Full CBR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CBR3 p.Ser2Leu Uncertain significance ★ ⚠ same residue
CBR3 p.Ala225Val Uncertain significance ★ ⚠ same type
CBR3 p.Ala41Thr Uncertain significance ★ ⚠ same type
CBR3 p.Arg211Cys Uncertain significance ★ ⚠ same type
CBR3 p.Asn181His Uncertain significance ★ ⚠ same type
CBR3 p.Asn90Lys Uncertain significance ★ ⚠ same type
CBR3 p.Asp63Ala Uncertain significance ★ same type
CBR3 p.Asp63Gly 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/cbr3-p-ser2trp (accessed [today's date]).

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