Is PDIA5 p.Ser19Pro (c.55T>C) pathogenic?

PDIA5 p.Ser19Pro (c.55T>C) is classified Uncertain significance in PDIA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-17). AlphaMissense: likely benign (0.071); Absent from gnomAD v4.1.

How common is PDIA5 p.Ser19Pro (c.55T>C) in the general population?

PDIA5 p.Ser19Pro (c.55T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDIA5 p.Ser19Pro (c.55T>C)?

AlphaMissense predicts likely benign (score 0.071) — an in-silico prediction, not a clinical call.

PDIA5 p.Ser19Pro

c.55T>C · rs2473278908 · VCV2307943

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.071 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.071	likely benign
REVEL	0.041	moderately benign-leaning
SaProt	LLR -6.05	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 -0.33	GERP -5.4
Regional constraint	o/e 0.97	unconstrained · MANE · 95 kb · p 0.49 · regional, not allelic
Overall
CADD	0.063	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: PDIA5
Protein: p.Ser19Pro
Coding: c.55T>C
MANE Select: NM_006810
dbSNP: rs2473278908
Type: single nucleotide variant
Location: chr3:123089180 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49 · 1 PDB

Full PDIA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDIA5 p.Ala133Val Uncertain significance ★ ⚠ same type
PDIA5 p.Ala150Val Uncertain significance ★ ⚠ same type
PDIA5 p.Ala179Val Uncertain significance ★ ⚠ same type
PDIA5 p.Ala334Pro Uncertain significance ★ ⚠ same type
PDIA5 p.Ala342Gly Uncertain significance ★ ⚠ same type
PDIA5 p.Ala365Thr Uncertain significance ★ ⚠ same type
PDIA5 p.Ala384Asp Uncertain significance ★ ⚠ same type
PDIA5 p.Ala469Gly 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/pdia5-p-ser19pro (accessed [today's date]).

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