Is PDCD11 p.Ala756Ser (c.2266G>T) pathogenic?

PDCD11 p.Ala756Ser (c.2266G>T) is classified Uncertain significance in PDCD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.2379); Absent from gnomAD v4.1.

How common is PDCD11 p.Ala756Ser (c.2266G>T) in the general population?

PDCD11 p.Ala756Ser (c.2266G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDCD11 p.Ala756Ser (c.2266G>T)?

AlphaMissense predicts likely benign (score 0.2379) — an in-silico prediction, not a clinical call.

PDCD11 p.Ala756Ser

c.2266G>T · VCV4133571

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2379 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2379	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -9.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 1.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 47 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	23.5	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 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.Ala756Ser
Coding: c.2266G>T
MANE Select: NM_014976
Type: single nucleotide variant
Location: chr10:103419697 (GRCh38)
Gene constraint: LOEUF 0.573 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.40 · 1 PDB
Residue 756: the s1 motif 8 domain

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

Similar variants

PDCD11 p.Ala756Pro Uncertain significance ★ ⚠ same residue
PDCD11 p.Ala756Val Uncertain significance ★ ⚠ same residue
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

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-ala756ser (accessed [today's date]).

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