Is CRYZ p.Ser97Thr (c.290G>C) pathogenic?

CRYZ p.Ser97Thr (c.290G>C) is classified Uncertain significance in CRYZ (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely benign (0.1299); Ultra-rare (popmax 0.0561%, afr).

How common is CRYZ p.Ser97Thr (c.290G>C) in the general population?

CRYZ p.Ser97Thr (c.290G>C) is ultra-rare (popmax 0.0561%, afr) (gnomAD).

What do computational predictors say about CRYZ p.Ser97Thr (c.290G>C)?

AlphaMissense predicts likely benign (score 0.1299) — an in-silico prediction, not a clinical call.

CRYZ p.Ser97Thr

c.290G>C · rs371028828 · VCV3077927

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1299 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0561%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1299	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -8.11	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 -4.5	GERP -3.6
Regional constraint	o/e 1.03	unconstrained · MANE · 19 kb · p 0.57 · regional, not allelic
Overall
CADD	5.654	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0561% African / African-American · 42/74,868 alleles

Filtering AF 0.0426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0379%

Overall 0.00267% 43/1,611,728 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0561%	1,783
Remaining individualsnot grpmax-eligible	0.0016%	62,406

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.Ser97Thr
Coding: c.290G>C
MANE Select: NM_001889
dbSNP: rs371028828
Type: single nucleotide variant
Location: chr1:74719347 (GRCh38)
Gene constraint: LOEUF 1.547 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.95 · 1 PDB

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.Glu183Lys 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

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-ser97thr (accessed [today's date]).

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