Is CRYZ p.Glu183Lys (c.547G>A) pathogenic?

CRYZ p.Glu183Lys (c.547G>A) is classified Benign in CRYZ (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0717); Common (popmax 6.07%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CRYZ p.Glu183Lys (c.547G>A)?

AlphaMissense predicts likely benign (score 0.0717) — an in-silico prediction, not a clinical call.

CRYZ p.Glu183Lys

Q: How common is CRYZ p.Glu183Lys (c.547G>A) in the general population?

CRYZ p.Glu183Lys (c.547G>A) is common (popmax 6.07%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.547G>A · rs17095822 · VCV783288

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0717 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.07%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0717	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -9.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.056, phastCons 0.99
Regional constraint	o/e 1.03	unconstrained · MANE · 19 kb · p 0.57 · regional, not allelic
Overall
CADD	21.1	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

Grpmax group 6.07% African / African-American · 4,553/75,010 alleles

Filtering AF 5.92% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.86%

Overall 0.317% 5,115/1,613,862 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.07%	16
Remaining individualsnot grpmax-eligible	0.419%	239
Admixed American	0.352%	284
Middle Eastern	0.281%	356
Ashkenazi Jewishnot grpmax-eligible	0.0304%	3,289
South Asian	0.011%	9,107
European (non-Finnish)	0.00449%	22,261

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.Glu183Lys
Coding: c.547G>A
MANE Select: NM_001889
dbSNP: rs17095822
Type: single nucleotide variant
Location: chr1:74710181 (GRCh38)
Gene constraint: LOEUF 1.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.95 · 1 PDB
Residue 183: a UniProt-annotated variant site (in); an α-helix

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

Similar variants

CRYZ c.265-1G>A Likely benign ★★ same type
CRYZ p.Ala139Thr Uncertain significance ★ ⚠ same type
CRYZ p.Ala148Val Uncertain significance ★ ⚠ same type
CRYZ p.Ala164Thr Uncertain significance ★ ⚠ same type
CRYZ p.Ala2Pro Uncertain significance ★ ⚠ same type
CRYZ p.Arg138Gln Uncertain significance ★ ⚠ same type
CRYZ p.Arg138Gly Uncertain significance ★ ⚠ same type
CRYZ p.Arg242Gln 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-glu183lys (accessed [today's date]).

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