Is CRY2 p.Val211Met (c.631G>A) pathogenic?

CRY2 p.Val211Met (c.631G>A) is classified Uncertain significance in CRY2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely pathogenic (0.7304); Ultra-rare (popmax 0.02%, amr).

How common is CRY2 p.Val211Met (c.631G>A) in the general population?

CRY2 p.Val211Met (c.631G>A) is ultra-rare (popmax 0.02%, amr) (gnomAD).

What do computational predictors say about CRY2 p.Val211Met (c.631G>A)?

AlphaMissense predicts likely pathogenic (score 0.7304) — an in-silico prediction, not a clinical call.

CRY2 p.Val211Met

c.631G>A · VCV4827792

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7304 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7304	likely pathogenic
REVEL	0.216	benign-leaning
SaProt	LLR -12.97	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 23 kb · p 1.9e-08 · regional, not allelic
Overall
CADD	24.7	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 0.02% Admixed American · 12/60,012 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00898%

Overall 0.00124% 20/1,613,250 alleles · ultra-rare exomes 18/1,460,880 · genomes 2/152,370 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.02%	5,001
African / African-American	0.00533%	18,765
East Asian	0.00223%	44,884
European (non-Finnish)	0.000254%	393,301

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: CRY2
Protein: p.Val211Met
Coding: c.631G>A
MANE Select: NM_021117
Type: single nucleotide variant
Location: chr11:45861011 (GRCh38)
Gene constraint: LOEUF 0.596 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 85.42

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-val211met (accessed [today's date]).

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