Is CRYAA p.Phe17Ser (c.50T>C) pathogenic?

CRYAA p.Phe17Ser (c.50T>C) is classified Uncertain significance in CRYAA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-04). AlphaMissense: ambiguous (0.3997); Absent from gnomAD v4.1; Associated with cataract 9 multiple types.

What condition is associated with CRYAA p.Phe17Ser (c.50T>C)?

CRYAA p.Phe17Ser (c.50T>C) is associated with cataract 9 multiple types (ClinVar).

How common is CRYAA p.Phe17Ser (c.50T>C) in the general population?

CRYAA p.Phe17Ser (c.50T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRYAA p.Phe17Ser (c.50T>C)?

AlphaMissense predicts ambiguous (score 0.3997) — an in-silico prediction, not a clinical call.

CRYAA p.Phe17Ser

c.50T>C · rs148704068 · VCV2514624

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3997 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,064,882)

Conditions

cataract 9 multiple types

Computational evidence

Protein change
AlphaMissense	0.3997	ambiguous
REVEL	0.462	indeterminate
SaProt	LLR -5.86	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 4.4, phastCons 1
Regional constraint	o/e 0.13	constrained · MANE · 3,177 bp · p 1.9e-11 · regional, not allelic
Overall
CADD	24.2	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 1,064,882). 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.Phe17Ser
Coding: c.50T>C
MANE Select: NM_000394
dbSNP: rs148704068
Type: single nucleotide variant
Location: chr21:43169149 (GRCh38)
Structure: AlphaFold pLDDT 74.60 · 5 PDB
Residue 17: 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-phe17ser (accessed [today's date]).

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