Is CRYBB1 p.Ser10Trp (c.29C>G) pathogenic?

CRYBB1 p.Ser10Trp (c.29C>G) is classified Uncertain significance in CRYBB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-03). AlphaMissense: likely benign (0.2688); Ultra-rare (popmax 0.0604%, sas); Associated with Inborn genetic diseases.

What condition is associated with CRYBB1 p.Ser10Trp (c.29C>G)?

CRYBB1 p.Ser10Trp (c.29C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CRYBB1 p.Ser10Trp (c.29C>G) in the general population?

CRYBB1 p.Ser10Trp (c.29C>G) is ultra-rare (popmax 0.0604%, sas) (gnomAD).

What do computational predictors say about CRYBB1 p.Ser10Trp (c.29C>G)?

AlphaMissense predicts likely benign (score 0.2688) — an in-silico prediction, not a clinical call.

CRYBB1 p.Ser10Trp

c.29C>G · rs776964678 · VCV2368506

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2688 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0604%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.2688	likely benign
REVEL	0.329	indeterminate
SaProt	LLR -11.55	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.17	GERP 0.049, phastCons 0.19
Regional constraint	o/e 0.86	unconstrained · MANE · 17 kb · p 0.0069 · regional, not allelic
Overall
CADD	11.96	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 0.0604% South Asian · 55/91,084 alleles

Filtering AF 0.0476% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.043%

Overall 0.00353% 57/1,613,894 alleles · ultra-rare exomes 53/1,461,568 · genomes 4/152,326 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0604%	1,656
European (non-Finnish)	0.00017%	589,950

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: CRYBB1
Protein: p.Ser10Trp
Coding: c.29C>G
MANE Select: NM_001887
dbSNP: rs776964678
Type: single nucleotide variant
Location: chr22:26616291 (GRCh38)

Full CRYBB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/crybb1-p-ser10trp (accessed [today's date]).

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