Is CBR1 p.His6Asp (c.16C>G) pathogenic?

CBR1 p.His6Asp (c.16C>G) is classified Uncertain significance in CBR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-26). AlphaMissense: likely benign (0.1649); Ultra-rare (popmax 0.0162%, eas).

How common is CBR1 p.His6Asp (c.16C>G) in the general population?

CBR1 p.His6Asp (c.16C>G) is ultra-rare (popmax 0.0162%, eas) (gnomAD).

What do computational predictors say about CBR1 p.His6Asp (c.16C>G)?

AlphaMissense predicts likely benign (score 0.1649) — an in-silico prediction, not a clinical call.

CBR1 p.His6Asp

c.16C>G · VCV3263653

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1649 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0162%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1649	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -8.38	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 0.93	GERP 0.87
Regional constraint	o/e 0.98	unconstrained · MANE · 2,763 bp · p 0.69 · regional, not allelic
Overall
CADD	17.6	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 0.0162% East Asian · 7/43,264 alleles

Filtering AF 0.0075% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0053%

Overall 0.000506% 7/1,383,490 alleles · ultra-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: CBR1
Protein: p.His6Asp
Coding: c.16C>G
MANE Select: NM_001757
Type: single nucleotide variant
Location: chr21:36070131 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.88 · 6 PDB
Residue 6: an α-helix

Full CBR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CBR1 p.Thr197= Benign ★★ same type
CBR1 p.Ala209Thr Uncertain significance ★ ⚠ same type
CBR1 p.Ala255Val Uncertain significance ★ ⚠ same type
CBR1 p.Ala52Val Uncertain significance ★ ⚠ same type
CBR1 p.Arg119Gln Uncertain significance ★ ⚠ same type
CBR1 p.Arg159Cys Uncertain significance ★ ⚠ same type
CBR1 p.Arg159His Uncertain significance ★ ⚠ same type
CBR1 p.Arg232Lys 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/cbr1-p-his6asp (accessed [today's date]).

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