Is CRYAA p.Pro82Leu (c.245C>T) pathogenic?

CRYAA p.Pro82Leu (c.245C>T) is classified Uncertain significance in CRYAA (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely pathogenic (0.9548); Absent from gnomAD v4.1; Associated with cataract 9 multiple types.

What condition is associated with CRYAA p.Pro82Leu (c.245C>T)?

CRYAA p.Pro82Leu (c.245C>T) is associated with cataract 9 multiple types (ClinVar).

How common is CRYAA p.Pro82Leu (c.245C>T) in the general population?

CRYAA p.Pro82Leu (c.245C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRYAA p.Pro82Leu (c.245C>T)?

AlphaMissense predicts likely pathogenic (score 0.9548) — an in-silico prediction, not a clinical call.

CRYAA p.Pro82Leu

c.245C>T · rs200183640 · VCV340097

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9548 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 5,552)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 9 multiple types

Computational evidence

Protein change
AlphaMissense	0.9548	likely pathogenic
REVEL	0.837	moderately pathogenic-leaning
SaProt	LLR -11.91	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.13	constrained · MANE · 3,177 bp · p 1.9e-11 · regional, not allelic
Overall
CADD	29.3	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

No allele count reported in gnomAD v4.1 (AN 5,552). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CRYAA
Protein: p.Pro82Leu
Coding: c.245C>T
MANE Select: NM_000394
dbSNP: rs200183640
Type: single nucleotide variant
Location: chr21:43170572 (GRCh38)
Structure: AlphaFold pLDDT 74.60 · 5 PDB
Residue 82: a UniProt-annotated variant site (in ctrct9; uncertain significance); the shsp domain

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

Disease context

cataract 9 multiple types — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CRYAA p.Pro82= Benign ★★ same residue
CRYAA p.Pro82Arg Uncertain significance ★ ⚠ same residue
CRYAA p.Arg116Cys Pathogenic ★★ same condition
CRYAA p.Arg116His Pathogenic ★★ same condition
CRYAA p.Arg12Cys Pathogenic/Likely pathogenic ★★ same condition
CRYAA p.Arg21Gln Pathogenic ★★ ⚠ same condition
CRYAA p.Arg21Trp Pathogenic/Likely pathogenic ★★ same condition
CRYAA p.Arg54Cys Pathogenic/Likely pathogenic ★★ 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/cryaa-p-pro82leu (accessed [today's date]).

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