Is PER2 p.Met1007Thr (c.3020T>C) pathogenic?

PER2 p.Met1007Thr (c.3020T>C) is classified Likely benign in PER2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). AlphaMissense: likely benign (0.0496); Rare (popmax 0.631%, eas).

How common is PER2 p.Met1007Thr (c.3020T>C) in the general population?

PER2 p.Met1007Thr (c.3020T>C) is rare (popmax 0.631%, eas) (gnomAD).

What do computational predictors say about PER2 p.Met1007Thr (c.3020T>C)?

AlphaMissense predicts likely benign (score 0.0496) — an in-silico prediction, not a clinical call.

PER2 p.Met1007Thr

c.3020T>C · VCV4960752

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0496 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.631%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0496	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -3.58	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.006	GERP -2.9
Regional constraint	o/e 0.93	unconstrained · MANE · 32 kb · p 0.0048 · regional, not allelic
Overall
CADD	0.043	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 0.631% East Asian · 283/44,878 alleles

Filtering AF 0.57% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.547%

Overall 0.0268% 432/1,613,866 alleles · rare exomes 383/1,461,654 · genomes 49/152,212 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.631%	159
Ashkenazi Jewishnot grpmax-eligible	0.122%	822
South Asian	0.0681%	1,469
Remaining individualsnot grpmax-eligible	0.064%	1,562
Admixed American	0.00167%	60,026
European (non-Finnish)	0.000847%	117,999

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: PER2
Protein: p.Met1007Thr
Coding: c.3020T>C
MANE Select: NM_022817
Type: single nucleotide variant
Location: chr2:238253003 (GRCh38)
Gene constraint: LOEUF 0.67 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.96 · 4 PDB
Residue 1007: the 'interaction with pparg' region

Full PER2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PER2 p.Arg401His Uncertain significance ★★ ⚠ same type
PER2 p.Glu184Ala Uncertain significance ★★ ⚠ same type
PER2 p.Ala655= Benign ★★ same type
PER2 p.Arg401Cys Benign ★★ same type
PER2 p.Arg820= Likely benign ★★ same type
PER2 p.Cys1084Arg Likely benign ★★ same type
PER2 p.His476Asn Likely benign ★★ same type
PER2 p.Phe393= 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/per2-p-met1007thr (accessed [today's date]).

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