Is PRDX4 p.Pro12Ser (c.34C>T) pathogenic?

PRDX4 p.Pro12Ser (c.34C>T) is classified Uncertain significance in PRDX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-23). AlphaMissense: likely benign (0.0716); Very rare (popmax 0.00351%, afr).

How common is PRDX4 p.Pro12Ser (c.34C>T) in the general population?

PRDX4 p.Pro12Ser (c.34C>T) is very rare (popmax 0.00351%, afr) (gnomAD).

What do computational predictors say about PRDX4 p.Pro12Ser (c.34C>T)?

AlphaMissense predicts likely benign (score 0.0716) — an in-silico prediction, not a clinical call.

PRDX4 p.Pro12Ser

c.34C>T · VCV4571891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0716 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00351%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0716	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -6.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -2.1	GERP 0.06
Regional constraint	o/e 0.92	unconstrained · MANE · 7,486 bp · p 0.39 · regional, not allelic
Overall
CADD	8.891	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 0.00351% African / African-American · 2/57,055 alleles

Filtering AF 0.000581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000218%

Overall 0.000671% 8/1,192,195 alleles · very rare exomes 6/1,079,514 · genomes 2/112,681 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00351%	28,527
European (non-Finnish)	0.000677%	147,767

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: PRDX4
Protein: p.Pro12Ser
Coding: c.34C>T
MANE Select: NM_006406
Type: single nucleotide variant
Location: chrX:23667604 (GRCh38)
Structure: AlphaFold pLDDT 84.59 · 14 PDB

Full PRDX4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRDX4 p.Asp105Asn Benign ★★ ⚠ same type
PRDX4 p.Ala9Thr Uncertain significance ★ ⚠ same type
PRDX4 p.Arg107Cys Uncertain significance ★ ⚠ same type
PRDX4 p.Arg139Thr Uncertain significance ★ ⚠ same type
PRDX4 p.Asp179His Uncertain significance ★ ⚠ same type
PRDX4 p.Asp268Asn Uncertain significance ★ ⚠ same type
PRDX4 p.Asp71Tyr Uncertain significance ★ ⚠ same type
PRDX4 p.Glu39Gln 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/prdx4-p-pro12ser (accessed [today's date]).

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