Is PER3 p.Phe211Val (c.631T>G) pathogenic?

PER3 p.Phe211Val (c.631T>G) is classified Uncertain significance in PER3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-27). AlphaMissense: ambiguous (0.4606); Very rare (popmax 0.004%, afr).

How common is PER3 p.Phe211Val (c.631T>G) in the general population?

PER3 p.Phe211Val (c.631T>G) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about PER3 p.Phe211Val (c.631T>G)?

AlphaMissense predicts ambiguous (score 0.4606) — an in-silico prediction, not a clinical call.

PER3 p.Phe211Val

c.631T>G · VCV3887826

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4606 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Computational evidence

Protein change
AlphaMissense	0.4606	ambiguous
REVEL	0.447	indeterminate
SaProt	LLR -13.12	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.4	GERP 1.7, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 45 kb · p 0.002 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F210V vs ClinVar F211V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,928 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000372% 6/1,613,760 alleles · very rare exomes 5/1,461,566 · genomes 1/152,194 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,976
Remaining individualsnot grpmax-eligible	0.0032%	31,237
South Asian	0.0011%	91,088

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.Phe211Val
Coding: c.631T>G
MANE Select: NM_001377275
Type: single nucleotide variant
Location: chr1:7793995 (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-phe211val (accessed [today's date]).

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