Is PER1 p.Ser95Phe (c.284C>T) pathogenic?

PER1 p.Ser95Phe (c.284C>T) is classified Uncertain significance in PER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-26). AlphaMissense: ambiguous (0.4898); Very rare (popmax 0.0068%, nfe).

How common is PER1 p.Ser95Phe (c.284C>T) in the general population?

PER1 p.Ser95Phe (c.284C>T) is very rare (popmax 0.0068%, nfe) (gnomAD).

What do computational predictors say about PER1 p.Ser95Phe (c.284C>T)?

AlphaMissense predicts ambiguous (score 0.4898) — an in-silico prediction, not a clinical call.

PER1 p.Ser95Phe

c.284C>T · VCV3416990

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4898 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0068%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4898	ambiguous
REVEL	0.072	moderately benign-leaning
SaProt	LLR -8.87	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	phastCons 1
Overall
CADD	28.4	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 0.0068% European (non-Finnish) · 78/1,147,130 alleles

Filtering AF 0.00553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00512%

Overall 0.00515% 80/1,553,158 alleles · very rare exomes 79/1,400,938 · genomes 1/152,220 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0068%	14,707
Remaining individualsnot grpmax-eligible	0.00168%	59,682
South Asian	0.00122%	81,936

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: PER1
Protein: p.Ser95Phe
Coding: c.284C>T
MANE Select: NM_002616
Type: single nucleotide variant
Location: chr17:8150309 (GRCh38)
Gene constraint: LOEUF 0.839 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.59
Residue 95: the 'interaction with btrc' region; the 'disordered' region

Full PER1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PER1 p.Thr45= Benign ★★ same type
PER1 p.Val1027Ile Benign/Likely benign ★★ same type
PER1 p.Val240Ile Likely benign ★★ same type
PER1 p.Ala1008Asp Uncertain significance ★ ⚠ same type
PER1 p.Ala1017Thr Uncertain significance ★ ⚠ same type
PER1 p.Ala1022Thr Uncertain significance ★ ⚠ same type
PER1 p.Ala1025Thr Uncertain significance ★ ⚠ same type
PER1 p.Ala1111Val Uncertain significance ★ ⚠ 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/per1-p-ser95phe (accessed [today's date]).

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