Is PTF1A p.Ser263Pro (c.787T>C) pathogenic?

PTF1A p.Ser263Pro (c.787T>C) is classified Conflicting classifications of pathogenicity in PTF1A (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.1613); Common (popmax 84.3%, eas) — too common for a highly-penetrant pathogenic allele; Associated with pancreatic beta cell agenesis with neonatal diabetes mellitus.

What condition is associated with PTF1A p.Ser263Pro (c.787T>C)?

PTF1A p.Ser263Pro (c.787T>C) is associated with pancreatic beta cell agenesis with neonatal diabetes mellitus, permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome, pancreatic agenesis 2 (ClinVar).

What do computational predictors say about PTF1A p.Ser263Pro (c.787T>C)?

AlphaMissense predicts likely benign (score 0.1613) — an in-silico prediction, not a clinical call.

PTF1A p.Ser263Pro

Q: How common is PTF1A p.Ser263Pro (c.787T>C) in the general population?

PTF1A p.Ser263Pro (c.787T>C) is common (popmax 84.3%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.787T>C · rs7918487 · VCV130055

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.1613 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 84.3%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

pancreatic beta cell agenesis with neonatal diabetes mellitus

Computational evidence

Protein change
AlphaMissense	0.1613	likely benign
REVEL	0.357	indeterminate
SaProt	LLR -6.14	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.56, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,372 bp · p 0.85 · regional, not allelic
Overall
CADD	21.5	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 84.3% East Asian · 37,651/44,682 alleles

Filtering AF 83.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 83.3%

Overall 49.7% 788,277/1,587,168 alleles · common exomes 708,733/1,435,372 · genomes 79,544/151,796 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	84.3%	1
Admixed American	65%	2
Middle Eastern	60.7%	2
Ashkenazi Jewishnot grpmax-eligible	55.9%	2
African / African-American	55.9%	2
South Asian	53.6%	2
Remaining individualsnot grpmax-eligible	52.7%	2
European (non-Finnish)	46.8%	2
Finnishnot grpmax-eligible	44.2%	2
Amishnot grpmax-eligible	42.1%	2

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.Ser263Pro
Coding: c.787T>C
MANE Select: NM_178161
dbSNP: rs7918487
Type: single nucleotide variant
Location: chr10:23193706 (GRCh38)
Gene constraint: LOEUF 1.878 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.81
Residue 263: the 'disordered' region; a UniProt-annotated variant site (in)

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

Disease context

pancreatic beta cell agenesis with neonatal diabetes mellitus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: permanent neonatal diabetes mellitus-pancreatic and cerebellar agenesis syndrome pancreatic agenesis 2 permanent neonatal diabetes mellitus

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-ser263pro (accessed [today's date]).

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