Is PDCD11 p.His498Pro (c.1493A>C) pathogenic?

PDCD11 p.His498Pro (c.1493A>C) is classified Uncertain significance in PDCD11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-21). AlphaMissense: likely benign (0.1923); Absent from gnomAD v4.1.

How common is PDCD11 p.His498Pro (c.1493A>C) in the general population?

PDCD11 p.His498Pro (c.1493A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDCD11 p.His498Pro (c.1493A>C)?

AlphaMissense predicts likely benign (score 0.1923) — an in-silico prediction, not a clinical call.

PDCD11 p.His498Pro

c.1493A>C · rs1473795147 · VCV2520625

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1923 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1923	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -10.04	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.55	GERP -3.2, phastCons 0.001
Regional constraint	o/e 0.91	unconstrained · MANE · 47 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	12.13	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

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.His498Pro
Coding: c.1493A>C
MANE Select: NM_014976
dbSNP: rs1473795147
Type: single nucleotide variant
Location: chr10:103415126 (GRCh38)
Gene constraint: LOEUF 0.573 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.40 · 1 PDB
Residue 498: the s1 motif 5 domain

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-his498pro (accessed [today's date]).

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