Is PER3 p.Ser114Arg (c.342T>A) pathogenic?

PER3 p.Ser114Arg (c.342T>A) is classified Uncertain significance in PER3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-11). AlphaMissense: ambiguous (0.4229); Very rare (popmax 0.005%, amr).

How common is PER3 p.Ser114Arg (c.342T>A) in the general population?

PER3 p.Ser114Arg (c.342T>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about PER3 p.Ser114Arg (c.342T>A)?

AlphaMissense predicts ambiguous (score 0.4229) — an in-silico prediction, not a clinical call.

PER3 p.Ser114Arg

c.342T>A · VCV3417040

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4229 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4229	ambiguous
REVEL	0.12	moderately benign-leaning
SaProt	LLR -9.34	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.91	GERP -3.4, phastCons 0.013
Regional constraint	o/e 1.09	unconstrained · MANE · 45 kb · p 0.002 · regional, not allelic
Overall
CADD	17.13	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 0.005% Admixed American · 3/59,984 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00031% 5/1,611,988 alleles · very rare exomes 3/1,459,838 · genomes 2/152,150 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,995
Remaining individualsnot grpmax-eligible	0.0032%	31,219

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.Ser114Arg
Coding: c.342T>A
MANE Select: NM_001377275
Type: single nucleotide variant
Location: chr1:7786788 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.62

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

Similar variants

PER3 p.Arg157His Uncertain significance ★★ ⚠ same type
PER3 p.Asn572Thr Uncertain significance ★★ ⚠ same type
PER3 p.Ala980= Benign ★★ same type
PER3 p.Cys1185Ser Benign ★★ same type
PER3 p.Ile614= Benign ★★ same type
PER3 p.Leu937= Likely benign ★★ same type
PER3 p.Thr527Ala Likely benign ★★ same type
PER3 p.Thr983= Benign/Likely 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/per3-p-ser114arg (accessed [today's date]).

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