Is PTF1A p.Pro247Arg (c.740C>G) pathogenic?

PTF1A p.Pro247Arg (c.740C>G) is classified Uncertain significance in PTF1A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-14). AlphaMissense: likely benign (0.1052); Ultra-rare (popmax 0.03%, mid); Associated with Inborn genetic diseases.

What condition is associated with PTF1A p.Pro247Arg (c.740C>G)?

PTF1A p.Pro247Arg (c.740C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PTF1A p.Pro247Arg (c.740C>G) in the general population?

PTF1A p.Pro247Arg (c.740C>G) is ultra-rare (popmax 0.03%, mid) (gnomAD).

What do computational predictors say about PTF1A p.Pro247Arg (c.740C>G)?

AlphaMissense predicts likely benign (score 0.1052) — an in-silico prediction, not a clinical call.

PTF1A p.Pro247Arg

c.740C>G · VCV3427460

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1052 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1052	likely benign
REVEL	0.2	benign-leaning
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.052	GERP -1.7, phastCons 0.001
Regional constraint	o/e 1.01	unconstrained · MANE · 1,372 bp · p 0.85 · regional, not allelic
Overall
CADD	15.53	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 0.03% Middle Eastern · 1/3,334 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00106%

Overall 0.00217% 27/1,246,990 alleles · ultra-rare exomes 25/1,095,614 · genomes 2/151,376 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.03%	3,334
Finnishnot grpmax-eligible	0.0127%	7,865
Remaining individualsnot grpmax-eligible	0.00434%	23,035
European (non-Finnish)	0.00199%	50,191

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.Pro247Arg
Coding: c.740C>G
MANE Select: NM_178161
Type: single nucleotide variant
Location: chr10:23193270 (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.Pro247Leu Uncertain significance ★ ⚠ 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-pro247arg (accessed [today's date]).

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