Is CRYBB1 p.Ala103Pro (c.307G>C) pathogenic?

CRYBB1 p.Ala103Pro (c.307G>C) is classified Uncertain significance in CRYBB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-22). AlphaMissense: likely pathogenic (0.9693); Absent from gnomAD v4.1.

How common is CRYBB1 p.Ala103Pro (c.307G>C) in the general population?

CRYBB1 p.Ala103Pro (c.307G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRYBB1 p.Ala103Pro (c.307G>C)?

AlphaMissense predicts likely pathogenic (score 0.9693) — an in-silico prediction, not a clinical call.

CRYBB1 p.Ala103Pro

c.307G>C · rs757351043 · VCV1310374

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9693 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9693	likely pathogenic
REVEL	0.613	indeterminate
SaProt	LLR -14.63	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.4	phastCons 0.76
Regional constraint	o/e 0.86	unconstrained · MANE · 17 kb · p 0.0069 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CRYBB1
Protein: p.Ala103Pro
Coding: c.307G>C
MANE Select: NM_001886 · reported on NM_001887
dbSNP: rs757351043
Type: single nucleotide variant
Location: chr22:26608014 (GRCh38)

Full CRYBB1 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/crybb1-p-ala103pro (accessed [today's date]).

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