Is CRYBA4 p.Pro11Thr (c.31C>A) pathogenic?

CRYBA4 p.Pro11Thr (c.31C>A) is classified Uncertain significance in CRYBA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-17). AlphaMissense: likely benign (0.0891); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CRYBA4 p.Pro11Thr (c.31C>A)?

CRYBA4 p.Pro11Thr (c.31C>A) is associated with Inborn genetic diseases (ClinVar).

How common is CRYBA4 p.Pro11Thr (c.31C>A) in the general population?

CRYBA4 p.Pro11Thr (c.31C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRYBA4 p.Pro11Thr (c.31C>A)?

AlphaMissense predicts likely benign (score 0.0891) — an in-silico prediction, not a clinical call.

CRYBA4 p.Pro11Thr

c.31C>A · rs2517431150 · VCV3077708

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0891 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0891	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -8.87	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 6.9	GERP 1.2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 7,887 bp · p 0.027 · regional, not allelic
Overall
CADD	19.66	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

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: CRYBA4
Protein: p.Pro11Thr
Coding: c.31C>A
MANE Select: NM_001886
dbSNP: rs2517431150
Type: single nucleotide variant
Location: chr22:26622627 (GRCh38)
Gene constraint: LOEUF 1.238 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.64 · 1 PDB
Residue 11: the 'n-terminal arm' region

Full CRYBA4 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

Similar variants

CRYBA4 p.Ile109Val Uncertain significance ★★ ⚠ same condition
CRYBA4 p.Phe29Leu Uncertain significance ★★ ⚠ same condition
CRYBB1 p.Ala98Glu Uncertain significance ★★ ⚠ same condition
CRYBB1 p.Arg132Cys Uncertain significance ★★ ⚠ same condition
CRYBB1 p.Arg231His Uncertain significance ★★ ⚠ same condition
CRYBB1 p.Lys150Glu Uncertain significance ★★ ⚠ same condition
CRYBB1 p.Ser130Thr Uncertain significance ★★ ⚠ same condition
CRYBB1 p.Trp193Cys Uncertain significance ★★ ⚠ same condition

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/cryba4-p-pro11thr (accessed [today's date]).

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