Is CRYAA p.Tyr18= (c.54C>T) pathogenic?

CRYAA p.Tyr18= (c.54C>T) is classified Benign in CRYAA (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-15). Low-frequency (popmax 4.74%, afr); Associated with cataract 9 multiple types.

What condition is associated with CRYAA p.Tyr18= (c.54C>T)?

CRYAA p.Tyr18= (c.54C>T) is associated with cataract 9 multiple types (ClinVar).

How common is CRYAA p.Tyr18= (c.54C>T) in the general population?

CRYAA p.Tyr18= (c.54C>T) is low-frequency (popmax 4.74%, afr) (gnomAD).

CRYAA p.Tyr18=

c.54C>T · rs61729442 · VCV466610

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 4.74%, afr)

Conditions

cataract 9 multiple types

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.15	GERP 3.4, phastCons 0.96
Overall
CADD	7.793	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.74% African / African-American · 1,582/33,380 alleles

Filtering AF 4.55% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.47%

Overall 0.175% 1,866/1,063,606 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.74%	21
Remaining individualsnot grpmax-eligible	0.357%	280
Admixed American	0.23%	434
Middle Eastern	0.19%	527
South Asian	0.00747%	13,394
European (non-Finnish)	0.00159%	62,702

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CRYAA
Protein: p.Tyr18=
Coding: c.54C>T
MANE Select: NM_000394
dbSNP: rs61729442
Type: single nucleotide variant
Location: chr21:43169153 (GRCh38)
Structure: AlphaFold pLDDT 74.60 · 5 PDB
Residue 18: a functional site (susceptible to oxidation); a UniProt-annotated variant site (in ctrct9; uncertain significance); the 'required for complex formation with bfsp1 and bfsp2; during homooligomerization, mediates the association of 2 dimers to form a tetramer' region

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-tyr18 (accessed [today's date]).

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