Is PDCD11 p.Ala709Pro (c.2125G>C) pathogenic?

PDCD11 p.Ala709Pro (c.2125G>C) is classified Uncertain significance in PDCD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-16). AlphaMissense: likely pathogenic (0.7582); Very rare (popmax 0.00501%, amr).

How common is PDCD11 p.Ala709Pro (c.2125G>C) in the general population?

PDCD11 p.Ala709Pro (c.2125G>C) is very rare (popmax 0.00501%, amr) (gnomAD).

What do computational predictors say about PDCD11 p.Ala709Pro (c.2125G>C)?

AlphaMissense predicts likely pathogenic (score 0.7582) — an in-silico prediction, not a clinical call.

PDCD11 p.Ala709Pro

c.2125G>C · VCV3887111

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7582 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00501%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7582	likely pathogenic
REVEL	0.171	moderately benign-leaning
SaProt	LLR -9.20	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -0.71, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 47 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00501% Admixed American · 3/59,930 alleles

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

Overall 0.000434% 7/1,613,638 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00501%	19,977
African / African-American	0.00267%	37,455
Remaining individualsnot grpmax-eligible	0.0016%	62,474
South Asian	0.0011%	91,006

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: PDCD11
Protein: p.Ala709Pro
Coding: c.2125G>C
MANE Select: NM_014976
Type: single nucleotide variant
Location: chr10:103419556 (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.Ala709Gly 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
PDCD11 p.Ala1605Glu 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-ala709pro (accessed [today's date]).

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