Is PDCD11 p.Ala2Val (c.5C>T) pathogenic?

PDCD11 p.Ala2Val (c.5C>T) is classified Uncertain significance in PDCD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-27). AlphaMissense: likely benign (0.2432); Very rare (popmax 0.00272%, nfe).

How common is PDCD11 p.Ala2Val (c.5C>T) in the general population?

PDCD11 p.Ala2Val (c.5C>T) is very rare (popmax 0.00272%, nfe) (gnomAD).

What do computational predictors say about PDCD11 p.Ala2Val (c.5C>T)?

AlphaMissense predicts likely benign (score 0.2432) — an in-silico prediction, not a clinical call.

PDCD11 p.Ala2Val

c.5C>T · rs560438483 · VCV3210550

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2432 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00272%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2432	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -7.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP 2.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 47 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	23.8	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

Grpmax group 0.00272% European (non-Finnish) · 32/1,178,362 alleles

Filtering AF 0.00197% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00211% 34/1,612,210 alleles · very rare exomes 31/1,460,010 · genomes 3/152,200 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00272%	36,824
Admixed American	0.00167%	59,996
African / African-American	0.00134%	74,882

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.Ala2Val
Coding: c.5C>T
MANE Select: NM_014976
dbSNP: rs560438483
Type: single nucleotide variant
Location: chr10:103398431 (GRCh38)
Gene constraint: LOEUF 0.573 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.40 · 1 PDB
Residue 2: the 'disordered' region; a modified residue (n-acetylalanine)

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-ala2val (accessed [today's date]).

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