Is PTF1A p.Ser54= (c.162C>T) pathogenic?

PTF1A p.Ser54= (c.162C>T) is classified Conflicting classifications of pathogenicity in PTF1A (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-23). Low-frequency (popmax 3.27%, sas); Associated with permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome.

How common is PTF1A p.Ser54= (c.162C>T) in the general population?

PTF1A p.Ser54= (c.162C>T) is low-frequency (popmax 3.27%, sas) (gnomAD).

PTF1A p.Ser54=

Q: What condition is associated with PTF1A p.Ser54= (c.162C>T)?

PTF1A p.Ser54= (c.162C>T) is associated with permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome (ClinVar).

c.162C>T · rs117678424 · VCV299622

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.27%, sas)

Conditions

permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.97	GERP 0.063, phastCons 1
Overall
CADD	10.14	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.27% South Asian · 2,905/88,948 alleles

Filtering AF 3.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.13%

Overall 0.29% 4,607/1,588,030 alleles · low-frequency exomes 4,221/1,435,864 · genomes 386/152,166 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	3.27%	31
East Asian	3.19%	31
Remaining individualsnot grpmax-eligible	0.456%	219
Middle Eastern	0.183%	546
African / African-American	0.033%	3,035
Admixed American	0.0258%	3,869
European (non-Finnish)	0.00299%	33,437

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.Ser54=
Coding: c.162C>T
MANE Select: NM_178161
dbSNP: rs117678424
Type: single nucleotide variant
Location: chr10:23192692 (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

permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PTF1A p.Pro191Thr Pathogenic/Likely pathogenic ★★ same condition
PTF1A p.Ala149Val Uncertain significance ★★ ⚠ same condition
PTF1A p.Ala3Val Uncertain significance ★★ ⚠ same condition
PTF1A p.Arg206Leu Uncertain significance ★★ ⚠ same condition
PTF1A p.Cys121Tyr Uncertain significance ★★ ⚠ same condition
PTF1A p.Gly88Asp Uncertain significance ★★ ⚠ same condition
PTF1A p.Leu89Ile Uncertain significance ★★ ⚠ same condition
PTF1A c.*15G>A Benign/Likely benign ★★ 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-ser54 (accessed [today's date]).

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