Is CRYZ p.Tyr205= (c.615C>T) pathogenic?

CRYZ p.Tyr205= (c.615C>T) is classified Benign in CRYZ (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-06). Common (popmax 15.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with CRYZ-related disorder.

What condition is associated with CRYZ p.Tyr205= (c.615C>T)?

CRYZ p.Tyr205= (c.615C>T) is associated with CRYZ-related disorder (ClinVar).

CRYZ p.Tyr205=

Q: How common is CRYZ p.Tyr205= (c.615C>T) in the general population?

CRYZ p.Tyr205= (c.615C>T) is common (popmax 15.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.615C>T · rs57413593 · VCV3037236

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 15.3%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

CRYZ-related disorder

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 0.079	GERP -3.5, phastCons 0.011
Overall
CADD	3.119	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.3% African / African-American · 11,473/74,886 alleles

Filtering AF 15.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 15%

Overall 0.899% 14,500/1,612,774 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	15.3%	7
Ashkenazi Jewishnot grpmax-eligible	3.47%	29
Remaining individualsnot grpmax-eligible	1.28%	78
Admixed American	1.01%	99
Middle Eastern	0.762%	131
European (non-Finnish)	0.0436%	2,294
South Asian	0.0418%	2,393
Finnishnot grpmax-eligible	0.00313%	31,975

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: CRYZ
Protein: p.Tyr205=
Coding: c.615C>T
MANE Select: NM_001889
dbSNP: rs57413593
Type: single nucleotide variant
Location: chr1:74710113 (GRCh38)
Gene constraint: LOEUF 1.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.95 · 1 PDB
Residue 205: an α-helix

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

Disease context

CRYZ-related disorder

Similar variants

CRYZ p.Gln280Arg Likely benign same condition
CRYZ p.Glu253= Benign same condition
CRYZ p.Gly289= Likely benign same condition
CRYZ p.Ile40= Likely benign same condition
CRYZ c.265-1G>A Likely benign ★★ same type
CRYZ p.Glu183Lys Benign ★★ same type
CRYZ p.Ala139Thr Uncertain significance ★ same type
CRYZ p.Ala148Val 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/cryz-p-tyr205 (accessed [today's date]).

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