Is CRYAA p.Arg68Trp (c.202C>T) pathogenic?

CRYAA p.Arg68Trp (c.202C>T) is classified Uncertain significance in CRYAA (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-10-13). AlphaMissense: ambiguous (0.5045); Absent from gnomAD v4.1; Associated with cataract 9 multiple types.

What condition is associated with CRYAA p.Arg68Trp (c.202C>T)?

CRYAA p.Arg68Trp (c.202C>T) is associated with cataract 9 multiple types (ClinVar).

How common is CRYAA p.Arg68Trp (c.202C>T) in the general population?

CRYAA p.Arg68Trp (c.202C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRYAA p.Arg68Trp (c.202C>T)?

AlphaMissense predicts ambiguous (score 0.5045) — an in-silico prediction, not a clinical call.

CRYAA p.Arg68Trp

c.202C>T · rs376164744 · VCV809292

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.5045 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 6,740)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

cataract 9 multiple types

Computational evidence

Protein change
AlphaMissense	0.5045	ambiguous
REVEL	0.757	pathogenic-leaning
SaProt	LLR -12.49	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.99	GERP -3.1, phastCons 1
Regional constraint	o/e 0.13	constrained · MANE · 3,177 bp · p 1.9e-11 · regional, not allelic
Overall
CADD	25.1	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

No allele count reported in gnomAD v4.1 (AN 6,740). 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.Arg68Trp
Coding: c.202C>T
MANE Select: NM_000394
dbSNP: rs376164744
Type: single nucleotide variant
Location: chr21:43170529 (GRCh38)
Structure: AlphaFold pLDDT 74.60 · 5 PDB
Residue 68: 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.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
CRYAA p.Gly98Arg Pathogenic ★★ same condition
CRYAA p.Ala155Asp 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/cryaa-p-arg68trp (accessed [today's date]).

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