Is PLEC p.Pro2642Ser (c.7924C>T) pathogenic?

PLEC p.Pro2642Ser (c.7924C>T) is classified Uncertain significance in PLEC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-28). AlphaMissense: likely benign (0.0909); Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with PLEC p.Pro2642Ser (c.7924C>T)?

PLEC p.Pro2642Ser (c.7924C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PLEC p.Pro2642Ser (c.7924C>T) in the general population?

PLEC p.Pro2642Ser (c.7924C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about PLEC p.Pro2642Ser (c.7924C>T)?

AlphaMissense predicts likely benign (score 0.0909) — an in-silico prediction, not a clinical call.

PLEC p.Pro2642Ser

c.7924C>T · rs782331341 · VCV3214715

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0909 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0909	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	phastCons 0.91
Regional constraint	o/e 1.08	unconstrained · MANE · 18 kb · p 4.9e-10 · regional, not allelic
Overall
CADD	8.136	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P2779S vs ClinVar P2642S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,966 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00025% 4/1,600,544 alleles · very rare exomes 4/1,448,174 · genomes 0/152,370 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,989
European (non-Finnish)	8.48e-05%	1,179,702

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: PLEC
Protein: p.Pro2642Ser
Coding: c.7924C>T
MANE Select: NM_201384
dbSNP: rs782331341
Type: single nucleotide variant
Location: chr8:143921897 (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.Pro2642Gln Uncertain significance ★★ ⚠ same residue
PLEC p.Pro2642Leu Uncertain significance ★★ ⚠ same residue
PLEC p.Pro2642= Conflicting classifications of pathogenicity ★ 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-pro2642ser (accessed [today's date]).

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