Is PLEC p.Arg1561Pro (c.4682G>C) pathogenic?

PLEC p.Arg1561Pro (c.4682G>C) is classified Uncertain significance in PLEC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: likely pathogenic (0.7779); No allele count reported in gnomAD v4.1 (AN 1,588,014); Associated with Inborn genetic diseases.

What condition is associated with PLEC p.Arg1561Pro (c.4682G>C)?

PLEC p.Arg1561Pro (c.4682G>C) is associated with Inborn genetic diseases (ClinVar).

How common is PLEC p.Arg1561Pro (c.4682G>C) in the general population?

PLEC p.Arg1561Pro (c.4682G>C) is no allele count reported in gnomAD v4.1 (AN 1,588,014) (gnomAD).

What do computational predictors say about PLEC p.Arg1561Pro (c.4682G>C)?

AlphaMissense predicts likely pathogenic (score 0.7779) — an in-silico prediction, not a clinical call.

PLEC p.Arg1561Pro

c.4682G>C · rs376840697 · VCV2553861

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7779 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,588,014)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7779	likely pathogenic
REVEL	0.434	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 18 kb · p 4.9e-10 · regional, not allelic
Overall
CADD	23.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R1698P vs ClinVar R1561P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,588,014). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PLEC
Protein: p.Arg1561Pro
Coding: c.4682G>C
MANE Select: NM_201384
dbSNP: rs376840697
Type: single nucleotide variant
Location: chr8:143925247 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PLEC p.Arg1561Gln Uncertain significance ★★ same residue
PLEC p.Arg1561Leu Uncertain significance ★ same residue
PLEC p.Arg1561= Likely benign ★ same residue
PLEC p.Ala1041Thr Uncertain significance ★★ ⚠ same condition
PLEC p.Ala1221Ser Uncertain significance ★★ ⚠ same condition
PLEC p.Ala1368Val Uncertain significance ★★ ⚠ same condition
PLEC p.Ala1390Val Uncertain significance ★★ ⚠ same condition
PLEC p.Ala1411Thr Uncertain significance ★★ ⚠ 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/plec-p-arg1561pro (accessed [today's date]).

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