Is PRDX1 p.Pro99Ser (c.295C>T) pathogenic?

PRDX1 p.Pro99Ser (c.295C>T) is classified Uncertain significance in PRDX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). AlphaMissense: likely benign (0.0959); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PRDX1 p.Pro99Ser (c.295C>T)?

PRDX1 p.Pro99Ser (c.295C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PRDX1 p.Pro99Ser (c.295C>T) in the general population?

PRDX1 p.Pro99Ser (c.295C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRDX1 p.Pro99Ser (c.295C>T)?

AlphaMissense predicts likely benign (score 0.0959) — an in-silico prediction, not a clinical call.

PRDX1 p.Pro99Ser

c.295C>T · VCV3937858

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0959 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0959	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -9.09	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 4.2	GERP 1.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,711 bp · p 0.37 · regional, not allelic
Overall
CADD	18.62	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: PRDX1
Protein: p.Pro99Ser
Coding: c.295C>T
MANE Select: NM_181697
Type: single nucleotide variant
Location: chr1:45514961 (GRCh38)
Gene constraint: LOEUF 1.322 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.29 · 20 PDB
Residue 99: the thioredoxin domain

Full PRDX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRDX1 p.Pro99= Likely benign ★ same residue
PRDX1 p.Asn101Ser Uncertain significance ★★ ⚠ same condition
PRDX1 p.Ile57Thr Uncertain significance ★★ ⚠ same condition
PRDX1 p.Val153Leu Uncertain significance ★★ ⚠ same condition
PRDX1 p.Ala121Thr Uncertain significance ★ ⚠ same condition
PRDX1 p.Ala86Pro Uncertain significance ★ ⚠ same condition
PRDX1 p.Arg110Cys Uncertain significance ★ ⚠ same condition
PRDX1 p.Arg151His Uncertain significance ★ ⚠ same condition

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/prdx1-p-pro99ser (accessed [today's date]).

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