Is PPCS p.Phe184fs (c.551del) pathogenic?

PPCS p.Phe184fs (c.551del) is classified Uncertain significance in PPCS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-17). Ultra-rare (popmax 0.0367%, amr).

How common is PPCS p.Phe184fs (c.551del) in the general population?

PPCS p.Phe184fs (c.551del) is ultra-rare (popmax 0.0367%, amr) (gnomAD).

PPCS p.Phe184fs

c.551del · rs757836367 · VCV1378341

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0367%, amr)

⚠ 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.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0367% Admixed American · 22/60,020 alleles

Filtering AF 0.0248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0209%

Overall 0.00149% 24/1,614,122 alleles · ultra-rare exomes 24/1,461,884 · genomes 0/152,238 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0367%	2,728
Remaining individualsnot grpmax-eligible	0.0032%	31,253

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.Phe184fs
Coding: c.551del
MANE Select: NM_024664
dbSNP: rs757836367
Type: Deletion
Location: chr1:42457287 (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-phe184fs (accessed [today's date]).

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