Is PPCS p.Gln12= (c.36G>A) pathogenic?

PPCS p.Gln12= (c.36G>A) is classified Benign in PPCS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Common (popmax 5.2%, afr) — too common for a highly-penetrant pathogenic allele.

PPCS p.Gln12=

Q: How common is PPCS p.Gln12= (c.36G>A) in the general population?

PPCS p.Gln12= (c.36G>A) is common (popmax 5.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.36G>A · rs72950587 · VCV1537987

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 5.2%, afr) — too common for a highly-penetrant pathogenic allele

⚠ 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 0.91	GERP -4.8, phastCons 0.42
Overall
CADD	6.121	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.2% African / African-American · 3,708/71,358 alleles

Filtering AF 5.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 5%

Overall 0.267% 4,033/1,513,260 alleles · common exomes 1,838/1,360,906 · genomes 2,195/152,354 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.2%	19
Admixed American	0.29%	345
Remaining individualsnot grpmax-eligible	0.273%	366
Middle Eastern	0.161%	622
South Asian	0.00787%	12,704
European (non-Finnish)	0.00247%	40,474

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.Gln12=
Coding: c.36G>A
MANE Select: NM_024664
dbSNP: rs72950587
Type: single nucleotide variant
Location: chr1:42456601 (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-gln12 (accessed [today's date]).

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