Is PER2 p.Ala695= (c.2085G>A) pathogenic?

PER2 p.Ala695= (c.2085G>A) is classified Likely benign in PER2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-01-13). Very rare (popmax 0.00661%, nfe); Associated with PER2-related disorder.

What condition is associated with PER2 p.Ala695= (c.2085G>A)?

PER2 p.Ala695= (c.2085G>A) is associated with PER2-related disorder (ClinVar).

How common is PER2 p.Ala695= (c.2085G>A) in the general population?

PER2 p.Ala695= (c.2085G>A) is very rare (popmax 0.00661%, nfe) (gnomAD).

PER2 p.Ala695=

c.2085G>A · rs141604367 · VCV3052018

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00661%, nfe)

Conditions

PER2-related disorder

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 -2.4	GERP -3.9
Overall
CADD	0.706	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00661% European (non-Finnish) · 78/1,180,042 alleles

Filtering AF 0.00538% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00498%

Overall 0.00533% 86/1,614,116 alleles · very rare exomes 83/1,461,878 · genomes 3/152,238 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00661%	15,129
African / African-American	0.00534%	18,736
Remaining individualsnot grpmax-eligible	0.0032%	31,242
South Asian	0.0022%	45,546

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: PER2
Protein: p.Ala695=
Coding: c.2085G>A
MANE Select: NM_022817
dbSNP: rs141604367
Type: single nucleotide variant
Location: chr2:238255892 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.96 · 4 PDB
Residue 695: the 'csnk1e binding domain' region

Full PER2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PER2-related disorder

Similar variants

PER2 p.Ala695Val Likely benign ★ same residue
PER2 c.3275-1G>A Uncertain significance ★ same condition
PER2 c.1153+10C>G Likely benign same condition
PER2 c.1542+4C>T Likely benign same condition
PER2 c.1775+4T>C Likely benign same condition
PER2 c.448+8G>T Likely benign same condition
PER2 p.Ala664= Benign same condition
PER2 p.Ala664Val Benign same condition

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/per2-p-ala695 (accessed [today's date]).

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