Is PEX19 p.Pro289Ser (c.865C>T) pathogenic?

PEX19 p.Pro289Ser (c.865C>T) is classified Uncertain significance in PEX19 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-07-25). AlphaMissense: likely benign (0.0578); Very rare (popmax 0.00167%, amr).

How common is PEX19 p.Pro289Ser (c.865C>T) in the general population?

PEX19 p.Pro289Ser (c.865C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about PEX19 p.Pro289Ser (c.865C>T)?

AlphaMissense predicts likely benign (score 0.0578) — an in-silico prediction, not a clinical call.

PEX19 p.Pro289Ser

c.865C>T · rs1223515137 · VCV593429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0578 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0578	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -7.43	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 7.1	GERP 1.8, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 5,570 bp · p 0.15 · regional, not allelic
Overall
CADD	21.2	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 0.00167% Admixed American · 1/60,036 alleles

Overall 0.000124% 2/1,614,168 alleles · very rare exomes 2/1,461,852 · genomes 0/152,316 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,036
European (non-Finnish)	8.47e-05%	1,180,013

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: PEX19
Protein: p.Pro289Ser
Coding: c.865C>T
MANE Select: NM_002857
dbSNP: rs1223515137
Type: single nucleotide variant
Location: chr1:160279586 (GRCh38)
Gene constraint: LOEUF 1.066 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.95 · 5 PDB

Full PEX19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PEX19 p.Pro289= Likely benign ★ same residue
PEX19 c.346+2T>C Likely pathogenic ★★ same type
PEX19 p.Leu94Ter Likely pathogenic ★★ same type
PEX19 p.Lys193Ter Pathogenic/Likely pathogenic ★★ same type
PEX19 p.Ser54Leu Pathogenic ★★ ⚠ same type
PEX19 c.*1335G>T Uncertain significance ★★ same type
PEX19 c.*864C>T Uncertain significance ★★ same type
PEX19 p.Ala14Pro 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/pex19-p-pro289ser (accessed [today's date]).

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