Is PABPN1 p.Pro57Ser (c.169C>T) pathogenic?

PABPN1 p.Pro57Ser (c.169C>T) is classified Uncertain significance in PABPN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-05-25). AlphaMissense: likely benign (0.1492); Very rare (popmax 0.00788%, amr); Associated with oculopharyngeal muscular dystrophy 1.

What condition is associated with PABPN1 p.Pro57Ser (c.169C>T)?

PABPN1 p.Pro57Ser (c.169C>T) is associated with oculopharyngeal muscular dystrophy 1 (ClinVar).

How common is PABPN1 p.Pro57Ser (c.169C>T) in the general population?

PABPN1 p.Pro57Ser (c.169C>T) is very rare (popmax 0.00788%, amr) (gnomAD).

How is Oculopharyngeal muscular dystrophy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about PABPN1 p.Pro57Ser (c.169C>T)?

AlphaMissense predicts likely benign (score 0.1492) — an in-silico prediction, not a clinical call.

PABPN1 p.Pro57Ser

c.169C>T · rs886042198 · VCV281604

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1492 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00788%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

oculopharyngeal muscular dystrophy 1

⚠ 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	0.1492	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -7.24	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.5	GERP 0.39, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 336 bp · p 0.88 · regional, not allelic
Overall
CADD	22.6	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 0.00788% Admixed American · 4/50,766 alleles

Filtering AF 0.00264% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00154%

Overall 0.000331% 5/1,509,948 alleles · very rare exomes 4/1,358,304 · genomes 1/151,644 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00788%	12,691
African / African-American	0.0014%	71,306

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: PABPN1
Protein: p.Pro57Ser
Coding: c.169C>T
MANE Select: NM_004643
dbSNP: rs886042198
Type: single nucleotide variant
Location: chr14:23321638 (GRCh38)

Full PABPN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

oculopharyngeal muscular dystrophy 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Oculopharyngeal muscular dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adult, Elderly
Prevalence: >1 / 1000 (Specific population)

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/pabpn1-p-pro57ser (accessed [today's date]).

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