Is PER2 p.Pro171Ser (c.511C>T) pathogenic?

PER2 p.Pro171Ser (c.511C>T) is classified Uncertain significance in PER2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-21). AlphaMissense: likely benign (0.1122); Very rare (popmax 0.00993%, nfe).

How common is PER2 p.Pro171Ser (c.511C>T) in the general population?

PER2 p.Pro171Ser (c.511C>T) is very rare (popmax 0.00993%, nfe) (gnomAD).

What do computational predictors say about PER2 p.Pro171Ser (c.511C>T)?

AlphaMissense predicts likely benign (score 0.1122) — an in-silico prediction, not a clinical call.

PER2 p.Pro171Ser

c.511C>T · VCV3887814

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1122 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00993%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1122	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -3.72	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 4.6	GERP -0.035, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 32 kb · p 0.0048 · regional, not allelic
Overall
CADD	12.19	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 0.00993% European (non-Finnish) · 117/1,178,258 alleles

Filtering AF 0.00844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00788%

Overall 0.00775% 125/1,612,080 alleles · very rare exomes 122/1,459,884 · genomes 3/152,196 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00993%	10,071
Remaining individualsnot grpmax-eligible	0.00801%	12,484
African / African-American	0.00401%	24,964

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.Pro171Ser
Coding: c.511C>T
MANE Select: NM_022817
Type: single nucleotide variant
Location: chr2:238273129 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.96 · 4 PDB

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

Similar variants

PER2 p.Arg401His Uncertain significance ★★ ⚠ same type
PER2 p.Glu184Ala Uncertain significance ★★ ⚠ same type
PER2 p.Ala655= Benign ★★ same type
PER2 p.Arg401Cys Benign ★★ same type
PER2 p.Arg820= Likely benign ★★ same type
PER2 p.Cys1084Arg Likely benign ★★ same type
PER2 p.His476Asn Likely benign ★★ same type
PER2 p.Phe393= Benign ★★ 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/per2-p-pro171ser (accessed [today's date]).

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