Is PER3 p.Ala172Val (c.515C>T) pathogenic?

PER3 p.Ala172Val (c.515C>T) is classified Uncertain significance in PER3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely benign (0.1542); Absent from gnomAD v4.1.

How common is PER3 p.Ala172Val (c.515C>T) in the general population?

PER3 p.Ala172Val (c.515C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PER3 p.Ala172Val (c.515C>T)?

AlphaMissense predicts likely benign (score 0.1542) — an in-silico prediction, not a clinical call.

PER3 p.Ala172Val

c.515C>T · VCV3417054

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1542 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1542	likely benign
REVEL	0.173	moderately benign-leaning
SaProt	LLR -8.22	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 2.2	GERP 0.12, phastCons 0.98
Regional constraint	o/e 1.09	unconstrained · MANE · 45 kb · p 0.002 · regional, not allelic
Overall
CADD	17.39	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PER3
Protein: p.Ala172Val
Coding: c.515C>T
MANE Select: NM_001377275
Type: single nucleotide variant
Location: chr1:7788169 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.62
Residue 172: the pas 1 domain

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-ala172val (accessed [today's date]).

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