Is CBR4 p.Arg120Ser (c.360G>T) pathogenic?

CBR4 p.Arg120Ser (c.360G>T) is classified Uncertain significance in CBR4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-26). AlphaMissense: likely pathogenic (0.6537); Ultra-rare (popmax 0.0164%, mid).

How common is CBR4 p.Arg120Ser (c.360G>T) in the general population?

CBR4 p.Arg120Ser (c.360G>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CBR4 p.Arg120Ser (c.360G>T)?

AlphaMissense predicts likely pathogenic (score 0.6537) — an in-silico prediction, not a clinical call.

CBR4 p.Arg120Ser

c.360G>T · VCV3263655

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6537 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6537	likely pathogenic
REVEL	0.17	moderately benign-leaning
SaProt	LLR -9.28	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -0.68, phastCons 0.48
Regional constraint	o/e 1.05	unconstrained · MANE · 20 kb · p 0.35 · regional, not allelic
Overall
CADD	19.32	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 0.0164% Middle Eastern · 1/6,080 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00539% 87/1,613,808 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,080
Admixed American	0.0117%	8,572
European (non-Finnish)	0.00644%	15,524
Remaining individualsnot grpmax-eligible	0.0048%	20,825

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: CBR4
Protein: p.Arg120Ser
Coding: c.360G>T
MANE Select: NM_032783
Type: single nucleotide variant
Location: chr4:169006795 (GRCh38)
Gene constraint: LOEUF 1.791 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.69 · 2 PDB
Residue 120: an α-helix

Full CBR4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CBR4 p.Arg120Lys Likely benign ★ same residue
PALLD c.2199+4C>T Uncertain significance ★★ same type
PALLD c.*110G>C Uncertain significance ★★ same type
PALLD c.*127C>G Uncertain significance ★★ same type
PALLD c.*135C>T Uncertain significance ★★ same type
PALLD c.*155C>G Uncertain significance ★★ same type
PALLD c.*161C>T Uncertain significance ★★ same type
PALLD c.*182T>A 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/cbr4-p-arg120ser (accessed [today's date]).

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