Is CRYGC p.Ser78Phe (c.233C>T) pathogenic?

CRYGC p.Ser78Phe (c.233C>T) is classified Likely pathogenic in CRYGC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-07). AlphaMissense: likely pathogenic (0.9754); Absent from gnomAD v4.1; Associated with CRYGC-related disorders.

What condition is associated with CRYGC p.Ser78Phe (c.233C>T)?

CRYGC p.Ser78Phe (c.233C>T) is associated with CRYGC-related disorders (ClinVar).

How common is CRYGC p.Ser78Phe (c.233C>T) in the general population?

CRYGC p.Ser78Phe (c.233C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CRYGC p.Ser78Phe (c.233C>T)?

AlphaMissense predicts likely pathogenic (score 0.9754) — an in-silico prediction, not a clinical call.

CRYGC p.Ser78Phe

c.233C>T · VCV4959522

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9754 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CRYGC-related disorders

Computational evidence

Protein change
AlphaMissense	0.9754	likely pathogenic ✓ concordant with ClinVar · top 2% in CRYGC
REVEL	0.959	strongly pathogenic-leaning
SaProt	LLR -15.75	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 11	GERP 2.5, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 1,586 bp · p 0.96 · regional, not allelic
Overall
CADD	29.6	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

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: CRYGC
Protein: p.Ser78Phe
Coding: c.233C>T
MANE Select: NM_020989
Type: single nucleotide variant
Location: chr2:208129460 (GRCh38)
Gene constraint: LOEUF 0.941 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 96.66 · 1 PDB
Residue 78: a UniProt-annotated variant site (in ctrct2; uncertain significance); a β-strand; the beta/gamma crystallin 'greek key' 2 domain

Full CRYGC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CRYGC-related disorders

Similar variants

CRYGC p.Tyr139Ter Pathogenic same condition
CRYGC p.Tyr144Ter Likely pathogenic same condition
CRYGC p.Arg168Gln Uncertain significance ⚠ same condition
CRYGC c.*9A>C Likely benign same condition
CRYGC p.Ala159fs Conflicting classifications of pathogenicity ★ same condition
CRYGC p.Gly53fs Likely pathogenic same condition
CRYGC p.Trp157Ter Pathogenic/Likely pathogenic ★★ same type
CRYGC p.Arg122His Uncertain significance ★★ ⚠ 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/crygc-p-ser78phe (accessed [today's date]).

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