Is PTF1A p.Arg152Pro (c.455G>C) pathogenic?

PTF1A p.Arg152Pro (c.455G>C) is classified Uncertain significance in PTF1A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: ambiguous (0.5613); Very rare (popmax 0.00108%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PTF1A p.Arg152Pro (c.455G>C)?

PTF1A p.Arg152Pro (c.455G>C) is associated with Inborn genetic diseases (ClinVar).

How common is PTF1A p.Arg152Pro (c.455G>C) in the general population?

PTF1A p.Arg152Pro (c.455G>C) is very rare (popmax 0.00108%, nfe) (gnomAD).

What do computational predictors say about PTF1A p.Arg152Pro (c.455G>C)?

AlphaMissense predicts ambiguous (score 0.5613) — an in-silico prediction, not a clinical call.

PTF1A p.Arg152Pro

c.455G>C · VCV4147034

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5613 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00108%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5613	ambiguous
REVEL	0.468	indeterminate
SaProt	LLR -9.09	tolerated
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.9	GERP -1.3, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,372 bp · p 0.85 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00108% European (non-Finnish) · 10/929,092 alleles

Filtering AF 0.000544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000397%

Overall 0.000881% 10/1,135,234 alleles · very rare exomes 8/987,168 · genomes 2/148,066 · joint denominator

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: PTF1A
Protein: p.Arg152Pro
Coding: c.455G>C
MANE Select: NM_178161
Type: single nucleotide variant
Location: chr10:23192985 (GRCh38)
Gene constraint: LOEUF 1.878 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.81

Full PTF1A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTF1A p.Arg152= Likely benign ★ same residue
PTF1A p.Ala149Val Uncertain significance ★★ ⚠ same condition
PTF1A p.Arg63Cys Uncertain significance ★★ ⚠ same condition
PTF1A p.Asp270His Uncertain significance ★★ ⚠ same condition
PTF1A p.Gly143Glu Uncertain significance ★★ ⚠ same condition
PTF1A p.Gly238Asp Uncertain significance ★★ ⚠ same condition
PTF1A p.His58Tyr Uncertain significance ★★ ⚠ same condition
PTF1A p.Pro275Leu Uncertain significance ★★ ⚠ same condition

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/ptf1a-p-arg152pro (accessed [today's date]).

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