Is PLEC p.Pro2636Ser (c.7906C>T) pathogenic?

PLEC p.Pro2636Ser (c.7906C>T) is classified Uncertain significance in PLEC (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-30). AlphaMissense: likely benign (0.0902); Very rare (popmax 0.000424%, nfe).

How common is PLEC p.Pro2636Ser (c.7906C>T) in the general population?

PLEC p.Pro2636Ser (c.7906C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about PLEC p.Pro2636Ser (c.7906C>T)?

AlphaMissense predicts likely benign (score 0.0902) — an in-silico prediction, not a clinical call.

PLEC p.Pro2636Ser

c.7906C>T · rs781931892 · VCV2434936

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0902 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0902	likely benign
REVEL	0.105	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 5.7	phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 18 kb · p 4.9e-10 · regional, not allelic
Overall
CADD	11.97	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 P2773S vs ClinVar P2636S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,179,794 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000313% 5/1,599,750 alleles · very rare exomes 4/1,447,512 · genomes 1/152,238 · joint denominator

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.Pro2636Ser
Coding: c.7906C>T
MANE Select: NM_201384
dbSNP: rs781931892
Type: single nucleotide variant
Location: chr8:143921915 (GRCh38)
Gene constraint: LOEUF 0.726 · pLI <0.01 (gnomAD)

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

Similar variants

PLEC p.Pro2636= Likely benign ★★ same residue
PLEC p.Arg1490Ter Pathogenic/Likely pathogenic ★★ same type
PLEC p.Arg1973Trp Pathogenic ★★ ⚠ same type
PLEC p.Arg2027Ter Pathogenic ★★ same type
PLEC p.Arg2292Ter Pathogenic ★★ same type
PLEC p.Arg2324Ter Pathogenic ★★ same type
PLEC p.Arg2394Ter Pathogenic ★★ same type
PLEC p.Arg559Ter Pathogenic ★★ 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/plec-p-pro2636ser (accessed [today's date]).

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