Is CRYAA p.Phe80Ser (c.239T>C) pathogenic?

CRYAA p.Phe80Ser (c.239T>C) is classified Uncertain significance in CRYAA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-22). AlphaMissense: likely pathogenic (0.9997); Absent from gnomAD v4.1; Associated with cataract 9 multiple types.

What condition is associated with CRYAA p.Phe80Ser (c.239T>C)?

CRYAA p.Phe80Ser (c.239T>C) is associated with cataract 9 multiple types (ClinVar).

How common is CRYAA p.Phe80Ser (c.239T>C) in the general population?

CRYAA p.Phe80Ser (c.239T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRYAA p.Phe80Ser (c.239T>C)?

AlphaMissense predicts likely pathogenic (score 0.9997) — an in-silico prediction, not a clinical call.

CRYAA p.Phe80Ser

c.239T>C · VCV3779181

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 9 multiple types

Computational evidence

Protein change
AlphaMissense	0.9997	likely pathogenic · top 1% in CRYAA
REVEL	0.938	strongly pathogenic-leaning
SaProt	LLR -12.78	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 7.6	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	32.0	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.Phe80Ser
Coding: c.239T>C
MANE Select: NM_000394
Type: single nucleotide variant
Location: chr21:43170566 (GRCh38)
Structure: AlphaFold pLDDT 74.60 · 5 PDB
Residue 80: 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-phe80ser (accessed [today's date]).

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