Is PPCS p.Arg242Ter (c.724C>T) pathogenic?

PPCS p.Arg242Ter (c.724C>T) is classified Uncertain significance in PPCS (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-23). Very rare (popmax 0.00267%, afr).

How common is PPCS p.Arg242Ter (c.724C>T) in the general population?

PPCS p.Arg242Ter (c.724C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

PPCS p.Arg242Ter

c.724C>T · rs1643354783 · VCV1364756

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

⚠ 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	nonsense (stop-gain)	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 6	GERP 2.3, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,906 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000372% 6/1,614,020 alleles · very rare exomes 5/1,461,834 · genomes 1/152,186 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,453
South Asian	0.0011%	91,084
European (non-Finnish)	0.000254%	393,349

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.Arg242Ter
Coding: c.724C>T
MANE Select: NM_024664
dbSNP: rs1643354783
Type: single nucleotide variant
Location: chr1:42459714 (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-arg242ter (accessed [today's date]).

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