Is CRYAA p.Pro82Arg (c.245C>G) pathogenic?

CRYAA p.Pro82Arg (c.245C>G) is classified Uncertain significance in CRYAA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-01). AlphaMissense: likely pathogenic (0.9745); Absent from gnomAD v4.1.

How common is CRYAA p.Pro82Arg (c.245C>G) in the general population?

CRYAA p.Pro82Arg (c.245C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRYAA p.Pro82Arg (c.245C>G)?

AlphaMissense predicts likely pathogenic (score 0.9745) — an in-silico prediction, not a clinical call.

CRYAA p.Pro82Arg

c.245C>G · rs200183640 · VCV2672891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9745 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9745	likely pathogenic
REVEL	0.845	moderately pathogenic-leaning
SaProt	LLR -13.19	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

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: CRYAA
Protein: p.Pro82Arg
Coding: c.245C>G
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

Similar variants

CRYAA p.Pro82= Benign ★★ same residue
CRYAA p.Pro82Leu Uncertain significance ★ ⚠ same residue
CRYAA p.Arg116Cys Pathogenic ★★ same type
CRYAA p.Arg116His Pathogenic ★★ same type
CRYAA p.Arg116Ser Pathogenic ★★ same type
CRYAA p.Arg12Cys Pathogenic/Likely pathogenic ★★ same type
CRYAA p.Arg21Gln Pathogenic ★★ ⚠ same type
CRYAA p.Arg21Trp Pathogenic/Likely pathogenic ★★ same type

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-pro82arg (accessed [today's date]).

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