Is PPCS p.Ser103= (c.309C>A) pathogenic?

PPCS p.Ser103= (c.309C>A) is classified Benign in PPCS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Common (popmax 5.19%, afr) — too common for a highly-penetrant pathogenic allele.

PPCS p.Ser103=

Q: How common is PPCS p.Ser103= (c.309C>A) in the general population?

PPCS p.Ser103= (c.309C>A) is common (popmax 5.19%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.309C>A · rs7524895 · VCV1566758

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 5.19%, afr) — too common for a highly-penetrant pathogenic allele

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 -0.85	GERP -4.3
Overall
CADD	2.497	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.19% African / African-American · 3,897/75,068 alleles

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

Overall 0.264% 4,261/1,613,328 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.19%	19
Remaining individualsnot grpmax-eligible	0.28%	357
Admixed American	0.24%	417
Middle Eastern	0.132%	758
South Asian	0.00878%	11,386
European (non-Finnish)	0.00246%	40,691

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.Ser103=
Coding: c.309C>A
MANE Select: NM_001395517 · reported on NM_024664
dbSNP: rs7524895
Type: single nucleotide variant
Location: chr1:42456874 (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-ser103 (accessed [today's date]).

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