Is PDIA5 p.Pro385Ser (c.1153C>T) pathogenic?

PDIA5 p.Pro385Ser (c.1153C>T) is classified Uncertain significance in PDIA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14). AlphaMissense: likely benign (0.0911); Ultra-rare (popmax 0.0184%, amr).

How common is PDIA5 p.Pro385Ser (c.1153C>T) in the general population?

PDIA5 p.Pro385Ser (c.1153C>T) is ultra-rare (popmax 0.0184%, amr) (gnomAD).

What do computational predictors say about PDIA5 p.Pro385Ser (c.1153C>T)?

AlphaMissense predicts likely benign (score 0.0911) — an in-silico prediction, not a clinical call.

PDIA5 p.Pro385Ser

c.1153C>T · VCV3416536

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0911 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0184%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0911	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -11.68	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.8	GERP 1.2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 95 kb · p 0.49 · regional, not allelic
Overall
CADD	22.7	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 0.0184% Admixed American · 11/59,888 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00787%

Overall 0.00726% 117/1,612,574 alleles · ultra-rare exomes 111/1,460,448 · genomes 6/152,126 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0184%	5,444
Middle Eastern	0.0165%	6,060
South Asian	0.00879%	11,374
European (non-Finnish)	0.00789%	12,678
Remaining individualsnot grpmax-eligible	0.0048%	20,812
African / African-American	0.00134%	74,868

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: PDIA5
Protein: p.Pro385Ser
Coding: c.1153C>T
MANE Select: NM_006810
Type: single nucleotide variant
Location: chr3:123150244 (GRCh38)
Gene constraint: LOEUF 0.898 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.49 · 1 PDB
Residue 385: the thioredoxin 3 domain

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-pro385ser (accessed [today's date]).

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