Is PER3 p.Thr978= (c.2934C>T) pathogenic?

PER3 p.Thr978= (c.2934C>T) is classified Benign in PER3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-17). Common (popmax 48.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with PER3-related disorder.

What condition is associated with PER3 p.Thr978= (c.2934C>T)?

PER3 p.Thr978= (c.2934C>T) is associated with PER3-related disorder (ClinVar).

PER3 p.Thr978=

Q: How common is PER3 p.Thr978= (c.2934C>T) in the general population?

PER3 p.Thr978= (c.2934C>T) is common (popmax 48.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2934C>T · rs2640908 · VCV3060144

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 48.7%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

PER3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -1.2
Overall
CADD	1.692	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 48.7% East Asian · 21,793/44,770 alleles

Filtering AF 48.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 47.9%

Overall 19.9% 319,833/1,609,316 alleles · common exomes 286,196/1,457,366 · genomes 33,637/151,950 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	48.7%	2
African / African-American	30.7%	3
South Asian	28.8%	3
Ashkenazi Jewishnot grpmax-eligible	24.3%	4
Middle Eastern	24%	4
Remaining individualsnot grpmax-eligible	22.1%	5
European (non-Finnish)	17.9%	6
Amishnot grpmax-eligible	17%	6
Admixed American	16.9%	6
Finnishnot grpmax-eligible	9.02%	11

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.Thr978=
Coding: c.2934C>T
MANE Select: NM_001377275
dbSNP: rs2640908
Type: single nucleotide variant
Location: chr1:7829881 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.62
Residue 978: the 'disordered' region; the '5 x 18 aa tandem repeats of s-[hp]-[ap]-t-[at]-[gst]-[atv]-l-s-[mt]-g-[ls]-p-p-[mrs]-[ekr]-[nst]-p' 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.Ala18Ser 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

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-thr978 (accessed [today's date]).

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