Is PER3 p.Ala18Ser (c.52G>T) pathogenic?

PER3 p.Ala18Ser (c.52G>T) is classified Likely benign in PER3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-28). AlphaMissense: likely benign (0.0903); Rare (popmax 0.176%, nfe); Associated with PER3-related disorder.

What condition is associated with PER3 p.Ala18Ser (c.52G>T)?

PER3 p.Ala18Ser (c.52G>T) is associated with PER3-related disorder (ClinVar).

How common is PER3 p.Ala18Ser (c.52G>T) in the general population?

PER3 p.Ala18Ser (c.52G>T) is rare (popmax 0.176%, nfe) (gnomAD).

What do computational predictors say about PER3 p.Ala18Ser (c.52G>T)?

AlphaMissense predicts likely benign (score 0.0903) — an in-silico prediction, not a clinical call.

PER3 p.Ala18Ser

c.52G>T · rs41278956 · VCV3041411

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0903 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.176%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PER3-related disorder

Computational evidence

Protein change
AlphaMissense	0.0903	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -6.44	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.4	GERP -1.9, phastCons 0.011
Regional constraint	o/e 1.09	unconstrained · MANE · 45 kb · p 0.002 · regional, not allelic
Overall
CADD	7.562	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 0.176% European (non-Finnish) · 2,035/1,155,040 alleles

Filtering AF 0.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.167%

Overall 0.141% 2,169/1,539,630 alleles · rare exomes 1,996/1,387,304 · genomes 173/152,326 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.09%	48
European (non-Finnish)grpmax	0.176%	568
Remaining individualsnot grpmax-eligible	0.125%	800
African / African-American	0.0289%	3,456
Finnishnot grpmax-eligible	0.016%	6,262
Admixed American	0.0145%	6,881
Ashkenazi Jewishnot grpmax-eligible	0.00747%	13,379
South Asian	0.00378%	26,454

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PER3
Protein: p.Ala18Ser
Coding: c.52G>T
MANE Select: NM_001377275
dbSNP: rs41278956
Type: single nucleotide variant
Location: chr1:7784929 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.62
Residue 18: the 'disordered' region

Full PER3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PER3-related disorder

Similar variants

PER3 c.275-9G>A Likely benign same condition
PER3 p.Ala163= Likely benign same condition
PER3 p.Gly1196= Likely benign same condition
PER3 p.Met1037Thr Likely benign same condition
PER3 p.Thr1019= Benign same condition
PER3 p.Thr306= Likely benign same condition
PER3 p.Thr626= Likely benign same condition
PER3 p.Thr978= 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/per3-p-ala18ser (accessed [today's date]).

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