Is PRDX5 p.Phe157Val (c.469T>G) pathogenic?

PRDX5 p.Phe157Val (c.469T>G) is classified Uncertain significance in PRDX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-27). AlphaMissense: likely pathogenic (0.7442); Ultra-rare (popmax 0.0121%, nfe).

How common is PRDX5 p.Phe157Val (c.469T>G) in the general population?

PRDX5 p.Phe157Val (c.469T>G) is ultra-rare (popmax 0.0121%, nfe) (gnomAD).

What do computational predictors say about PRDX5 p.Phe157Val (c.469T>G)?

AlphaMissense predicts likely pathogenic (score 0.7442) — an in-silico prediction, not a clinical call.

PRDX5 p.Phe157Val

c.469T>G · rs372183360 · VCV2346306

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7442 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7442	likely pathogenic
REVEL	0.515	indeterminate
SaProt	LLR -13.05	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 1.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 3,472 bp · p 0.56 · regional, not allelic
Overall
CADD	28.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.0121% European (non-Finnish) · 143/1,180,028 alleles

Filtering AF 0.0105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00981%

Overall 0.00892% 144/1,614,054 alleles · ultra-rare exomes 138/1,461,862 · genomes 6/152,192 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0121%	8,252
African / African-American	0.00133%	74,926

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: PRDX5
Protein: p.Phe157Val
Coding: c.469T>G
MANE Select: NM_012094
dbSNP: rs372183360
Type: single nucleotide variant
Location: chr11:64320895 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.13 · 12 PDB
Residue 157: a UniProt-annotated variant site (in a breast cancer sample; somatic mutation); the thioredoxin domain; an α-helix

Full PRDX5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRDX5 p.Ala192Thr Uncertain significance ★ ⚠ same type
PRDX5 p.Ala27Val Uncertain significance ★ ⚠ same type
PRDX5 p.Ala30Thr Uncertain significance ★ ⚠ same type
PRDX5 p.Arg176Gln Uncertain significance ★ ⚠ same type
PRDX5 p.Asn129Ile Uncertain significance ★ ⚠ same type
PRDX5 p.Gly107Glu Uncertain significance ★ ⚠ same type
PRDX5 p.Gly23Arg Uncertain significance ★ ⚠ same type
PRDX5 p.His104Gln 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/prdx5-p-phe157val (accessed [today's date]).

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