Is CBY3 p.Ser70Arg (c.210C>A) pathogenic?

CBY3 p.Ser70Arg (c.210C>A) is classified Uncertain significance in CBY3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-27). AlphaMissense: ambiguous (0.3934); Ultra-rare (popmax 0.0211%, nfe).

How common is CBY3 p.Ser70Arg (c.210C>A) in the general population?

CBY3 p.Ser70Arg (c.210C>A) is ultra-rare (popmax 0.0211%, nfe) (gnomAD).

What do computational predictors say about CBY3 p.Ser70Arg (c.210C>A)?

AlphaMissense predicts ambiguous (score 0.3934) — an in-silico prediction, not a clinical call.

CBY3 p.Ser70Arg

c.210C>A · rs760010939 · VCV2354327

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3934 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0211%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3934	ambiguous
REVEL	0.047	moderately benign-leaning
SaProt	LLR -5.53	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3	GERP 0.16, phastCons 0.99
Regional constraint	o/e 1.19	unconstrained · MANE · 2,332 bp · p 0.00053 · regional, not allelic
Overall
CADD	17.48	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 0.0211% European (non-Finnish) · 242/1,146,722 alleles

Filtering AF 0.0189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.018%

Overall 0.0164% 252/1,535,668 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0211%	4,739
Remaining individualsnot grpmax-eligible	0.0133%	7,493
Finnishnot grpmax-eligible	0.00224%	44,584
African / African-American	0.00137%	73,068

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: CBY3
Protein: p.Ser70Arg
Coding: c.210C>A
MANE Select: NM_001746 · reported on NM_001164444
dbSNP: rs760010939
Type: single nucleotide variant
Location: chr5:179679102 (GRCh38)

Full CBY3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/cby3-p-ser70arg (accessed [today's date]).

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