Is PPCS p.Leu177= (c.529C>T) pathogenic?

PPCS p.Leu177= (c.529C>T) is classified Likely benign in PPCS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-03). Very rare (popmax 0.00223%, eas).

How common is PPCS p.Leu177= (c.529C>T) in the general population?

PPCS p.Leu177= (c.529C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

PPCS p.Leu177=

c.529C>T · rs766664458 · VCV1651253

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.5	GERP -1.5, phastCons 1
Overall
CADD	10.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,882 alleles

Overall 0.000186% 3/1,614,004 alleles · very rare exomes 2/1,461,878 · genomes 1/152,126 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
Finnishnot grpmax-eligible	0.00156%	64,028
European (non-Finnish)	8.47e-05%	1,180,034

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.Leu177=
Coding: c.529C>T
MANE Select: NM_024664
dbSNP: rs766664458
Type: single nucleotide variant
Location: chr1:42457267 (GRCh38)

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

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-leu177 (accessed [today's date]).

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