Is PDCD11 p.Pro280Leu (c.839C>T) pathogenic?

PDCD11 p.Pro280Leu (c.839C>T) is classified Uncertain significance in PDCD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-22). AlphaMissense: likely pathogenic (0.8115); Absent from gnomAD v4.1.

How common is PDCD11 p.Pro280Leu (c.839C>T) in the general population?

PDCD11 p.Pro280Leu (c.839C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDCD11 p.Pro280Leu (c.839C>T)?

AlphaMissense predicts likely pathogenic (score 0.8115) — an in-silico prediction, not a clinical call.

PDCD11 p.Pro280Leu

c.839C>T · rs2540636775 · VCV2487761

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8115 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8115	likely pathogenic
REVEL	0.579	indeterminate
SaProt	LLR -12.78	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 47 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PDCD11
Protein: p.Pro280Leu
Coding: c.839C>T
MANE Select: NM_014976
dbSNP: rs2540636775
Type: single nucleotide variant
Location: chr10:103406759 (GRCh38)
Gene constraint: LOEUF 0.573 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.40 · 1 PDB

Full PDCD11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDCD11 p.Ala1131Gly Uncertain significance ★ ⚠ same type
PDCD11 p.Ala1202Val Uncertain significance ★ ⚠ same type
PDCD11 p.Ala1526Gly Uncertain significance ★ ⚠ same type
PDCD11 p.Ala1526Thr Uncertain significance ★ ⚠ same type
PDCD11 p.Ala1538Thr Uncertain significance ★ ⚠ same type
PDCD11 p.Ala1594Val Uncertain significance ★ ⚠ same type
PDCD11 p.Ala1605Glu Uncertain significance ★ ⚠ same type
PDCD11 p.Ala1605Thr Uncertain significance ★ ⚠ 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/pdcd11-p-pro280leu (accessed [today's date]).

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