Is PRDX5 p.Ser25Phe (c.74C>T) pathogenic?

PRDX5 p.Ser25Phe (c.74C>T) is classified Uncertain significance in PRDX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-30). AlphaMissense: likely benign (0.1133); Very rare (popmax 0.00517%, nfe).

How common is PRDX5 p.Ser25Phe (c.74C>T) in the general population?

PRDX5 p.Ser25Phe (c.74C>T) is very rare (popmax 0.00517%, nfe) (gnomAD).

What do computational predictors say about PRDX5 p.Ser25Phe (c.74C>T)?

AlphaMissense predicts likely benign (score 0.1133) — an in-silico prediction, not a clinical call.

PRDX5 p.Ser25Phe

c.74C>T · VCV3783127

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1133 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00517%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1133	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -7.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.76	GERP -2.9
Regional constraint	o/e 0.96	unconstrained · MANE · 3,472 bp · p 0.56 · regional, not allelic
Overall
CADD	7.99	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

Grpmax group 0.00517% European (non-Finnish) · 61/1,179,896 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.00397% 64/1,612,430 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00517%	19,343
Remaining individualsnot grpmax-eligible	0.00321%	31,157
African / African-American	0.00134%	74,882

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.Ser25Phe
Coding: c.74C>T
MANE Select: NM_012094
Type: single nucleotide variant
Location: chr11:64318289 (GRCh38)
Gene constraint: LOEUF 1.237 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.13 · 12 PDB

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

Similar variants

PRDX5 p.Ser25Pro Uncertain significance ★ ⚠ same residue
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

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-ser25phe (accessed [today's date]).

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