Is PPCS p.Asn167Ser (c.500A>G) pathogenic?

PPCS p.Asn167Ser (c.500A>G) is classified Uncertain significance in PPCS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely benign (0.0647); Very rare (popmax 0.00504%, amr).

How common is PPCS p.Asn167Ser (c.500A>G) in the general population?

PPCS p.Asn167Ser (c.500A>G) is very rare (popmax 0.00504%, amr) (gnomAD).

What do computational predictors say about PPCS p.Asn167Ser (c.500A>G)?

AlphaMissense predicts likely benign (score 0.0647) — an in-silico prediction, not a clinical call.

PPCS p.Asn167Ser

c.500A>G · rs750829177 · VCV1363084

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0647 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00504%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0647	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -4.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.75	GERP -4.2
Regional constraint	o/e 1.04	unconstrained · MANE · 687 bp · p 0.55 · regional, not allelic
Overall
CADD	0.878	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00504% Admixed American · 3/59,508 alleles

Filtering AF 0.00134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000671%

Overall 0.001% 16/1,596,228 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00504%	19,836
Remaining individualsnot grpmax-eligible	0.00161%	62,062
European (non-Finnish)	0.00102%	97,995

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.Asn167Ser
Coding: c.500A>G
MANE Select: NM_001395517 · reported on NM_024664
dbSNP: rs750829177
Type: single nucleotide variant
Location: chr1:42457065 (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-asn167ser (accessed [today's date]).

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