Is PPCS p.Leu30Val (c.88C>G) pathogenic?

PPCS p.Leu30Val (c.88C>G) is classified Uncertain significance in PPCS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely benign (0.1156); Very rare (popmax 0.0017%, amr); Associated with Inborn genetic diseases.

What condition is associated with PPCS p.Leu30Val (c.88C>G)?

PPCS p.Leu30Val (c.88C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PPCS p.Leu30Val (c.88C>G) in the general population?

PPCS p.Leu30Val (c.88C>G) is very rare (popmax 0.0017%, amr) (gnomAD).

What do computational predictors say about PPCS p.Leu30Val (c.88C>G)?

AlphaMissense predicts likely benign (score 0.1156) — an in-silico prediction, not a clinical call.

PPCS p.Leu30Val

c.88C>G · VCV3423378

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1156 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1156	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -10.36	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.38	GERP -3, phastCons 0.029
Regional constraint	o/e 1.04	unconstrained · MANE · 687 bp · p 0.55 · regional, not allelic
Overall
CADD	15.59	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 0.0017% Admixed American · 1/58,744 alleles

Filtering AF 0.000184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000501% 8/1,595,958 alleles · very rare exomes 7/1,443,760 · genomes 1/152,198 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0017%	58,744
South Asian	0.00113%	88,754
European (non-Finnish)	0.000511%	195,594

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: PPCS
Protein: p.Leu30Val
Coding: c.88C>G
MANE Select: NM_024664
Type: single nucleotide variant
Location: chr1:42456653 (GRCh38)

Full PPCS 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

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/ppcs-p-leu30val (accessed [today's date]).

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