Is CRY2 p.Arg29His (c.86G>A) pathogenic?

CRY2 p.Arg29His (c.86G>A) is classified Uncertain significance in CRY2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-24). AlphaMissense: likely pathogenic (0.9668); No allele count reported in gnomAD v4.1 (AN 1,600,630).

How common is CRY2 p.Arg29His (c.86G>A) in the general population?

CRY2 p.Arg29His (c.86G>A) is no allele count reported in gnomAD v4.1 (AN 1,600,630) (gnomAD).

What do computational predictors say about CRY2 p.Arg29His (c.86G>A)?

AlphaMissense predicts likely pathogenic (score 0.9668) — an in-silico prediction, not a clinical call.

CRY2 p.Arg29His

c.86G>A · VCV4234557

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9668 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,600,630)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9668	likely pathogenic
REVEL	0.923	moderately pathogenic-leaning
SaProt	LLR -13.69	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.16	constrained · MANE · 41 bp · p 0.00026 · regional, not allelic
Overall
CADD	34.0	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

No allele count reported in gnomAD v4.1 (AN 1,600,630). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CRY2
Protein: p.Arg29His
Coding: c.86G>A
MANE Select: NM_021117
Type: single nucleotide variant
Location: chr11:45847576 (GRCh38)
Gene constraint: LOEUF 0.596 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 85.42
Residue 29: the photolyase/cryptochrome alpha/beta domain

Full CRY2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CRY2 p.Ala12Glu Benign ★★ same type
CRY2 p.Gly269= Benign ★★ same type
CRY2 c.37G>C Uncertain significance ★ same type
CRY2 c.-5C>T Uncertain significance ★ same type
CRY2 p.Ala12Val Uncertain significance ★ ⚠ same type
CRY2 p.Ala14Glu Uncertain significance ★ ⚠ same type
CRY2 p.Ala14Val Uncertain significance ★ ⚠ same type
CRY2 p.Ala16Pro 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/cry2-p-arg29his (accessed [today's date]).

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