Is CNR2 p.Phe97= (c.291C>T) pathogenic?

CNR2 p.Phe97= (c.291C>T) is classified Likely benign in CNR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-29). Ultra-rare (popmax 0.036%, afr).

How common is CNR2 p.Phe97= (c.291C>T) in the general population?

CNR2 p.Phe97= (c.291C>T) is ultra-rare (popmax 0.036%, afr) (gnomAD).

CNR2 p.Phe97=

c.291C>T · rs144279977 · VCV737245

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.036%, afr)

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 0.79	GERP -4, phastCons 1
Overall
CADD	5.915	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.036% African / African-American · 27/74,940 alleles

Filtering AF 0.0254% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0219%

Overall 0.00186% 30/1,614,094 alleles · ultra-rare exomes 16/1,461,886 · genomes 14/152,208 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.036%	2,776
Admixed American	0.00167%	59,996
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	8.47e-05%	1,180,045

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: CNR2
Protein: p.Phe97=
Coding: c.291C>T
MANE Select: NM_001841
dbSNP: rs144279977
Type: single nucleotide variant
Location: chr1:23875327 (GRCh38)
Gene constraint: LOEUF 1.531 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 84.57 · 14 PDB

Full CNR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNR2 p.Arg66Gln Benign ★★ same type
CNR2 p.Cys313= Benign ★★ same type
CNR2 p.Ala199Thr Uncertain significance ★ ⚠ same type
CNR2 p.Ala328Val Uncertain significance ★ ⚠ same type
CNR2 p.Ala332Ser Uncertain significance ★ ⚠ same type
CNR2 p.Ala342Ser Uncertain significance ★ ⚠ same type
CNR2 p.Arg147Cys Uncertain significance ★ ⚠ same type
CNR2 p.Arg236Gln 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/cnr2-p-phe97 (accessed [today's date]).

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