Is PPT1 p.Gln91Pro (c.272A>C) pathogenic?

PPT1 p.Gln91Pro (c.272A>C) is classified Pathogenic/Likely pathogenic in PPT1 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-13). AlphaMissense: likely pathogenic (0.9454); Very rare (popmax 0.00891%, eas); Associated with neuronal ceroid lipofuscinosis.

What condition is associated with PPT1 p.Gln91Pro (c.272A>C)?

PPT1 p.Gln91Pro (c.272A>C) is associated with neuronal ceroid lipofuscinosis, neuronal ceroid lipofuscinosis 1 (ClinVar).

How common is PPT1 p.Gln91Pro (c.272A>C) in the general population?

PPT1 p.Gln91Pro (c.272A>C) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about PPT1 p.Gln91Pro (c.272A>C)?

AlphaMissense predicts likely pathogenic (score 0.9454) — an in-silico prediction, not a clinical call.

PPT1 p.Gln91Pro

c.272A>C · rs386833639 · VCV56187

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.9454 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neuronal ceroid lipofuscinosis

Computational evidence

Protein change
AlphaMissense	0.9454	likely pathogenic ✓ concordant with ClinVar · top 10% in PPT1
REVEL	0.989	strongly pathogenic-leaning
SaProt	LLR -14.34	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 23 kb · p 0.052 · regional, not allelic
Overall
CADD	28.2	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 0.00891% East Asian · 4/44,884 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00031% 5/1,613,994 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,221
Remaining individualsnot grpmax-eligible	0.0016%	62,482

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: PPT1
Protein: p.Gln91Pro
Coding: c.272A>C
MANE Select: NM_000310
dbSNP: rs386833639
Type: single nucleotide variant
Location: chr1:40092135 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.05 · 1 PDB
Residue 91: an α-helix

Full PPT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neuronal ceroid lipofuscinosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neuronal ceroid lipofuscinosis 1

Similar variants

PPT1 p.Gln91_Cys96delinsPhe Likely pathogenic same residue
PPT1 p.Gln91Glu Uncertain significance ★ ⚠ same residue
PPT1 c.234+1G>A Pathogenic ★★ same condition
PPT1 c.362+1G>A Likely pathogenic ★★ same condition
PPT1 c.433+1G>A Pathogenic ★★ same condition
PPT1 c.627+1G>T Likely pathogenic ★★ same condition
PPT1 c.628-1G>T Pathogenic ★★ same condition
PPT1 c.628-2A>G Pathogenic/Likely pathogenic ★★ 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/ppt1-p-gln91pro (accessed [today's date]).

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