Is PRDX1 p.Ala175Ser (c.523G>T) pathogenic?

PRDX1 p.Ala175Ser (c.523G>T) is classified Uncertain significance in PRDX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-06). AlphaMissense: ambiguous (0.363); Very rare (popmax 0.00837%, amr).

How common is PRDX1 p.Ala175Ser (c.523G>T) in the general population?

PRDX1 p.Ala175Ser (c.523G>T) is very rare (popmax 0.00837%, amr) (gnomAD).

What do computational predictors say about PRDX1 p.Ala175Ser (c.523G>T)?

AlphaMissense predicts ambiguous (score 0.363) — an in-silico prediction, not a clinical call.

PRDX1 p.Ala175Ser

c.523G>T · rs1643741191 · VCV1902458

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.363 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00837%, amr)

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.363	ambiguous
REVEL	0.61	indeterminate
SaProt	LLR -10.67	damaging
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,711 bp · p 0.37 · regional, not allelic
Overall
CADD	28.0	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 0.00837% Admixed American · 5/59,764 alleles

Filtering AF 0.00324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00031% 5/1,612,798 alleles · very rare exomes 3/1,460,690 · genomes 2/152,108 · joint denominator

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: PRDX1
Protein: p.Ala175Ser
Coding: c.523G>T
MANE Select: NM_181697
dbSNP: rs1643741191
Type: single nucleotide variant
Location: chr1:45511406 (GRCh38)

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

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-ala175ser (accessed [today's date]).

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