Is PPCS p.Ala173= (c.519G>A) pathogenic?

PPCS p.Ala173= (c.519G>A) is classified Conflicting classifications of pathogenicity in PPCS (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0671%, nfe).

How common is PPCS p.Ala173= (c.519G>A) in the general population?

PPCS p.Ala173= (c.519G>A) is ultra-rare (popmax 0.0671%, nfe) (gnomAD).

PPCS p.Ala173=

c.519G>A · rs200337358 · VCV1643066

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0671%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.325	indeterminate
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.4	GERP 2.4, phastCons 1
Overall
CADD	16.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0671% European (non-Finnish) · 792/1,180,006 alleles

Filtering AF 0.0632% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0617%

Overall 0.0602% 971/1,614,144 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.274%	366
European (non-Finnish)grpmax	0.0671%	1,490
Remaining individualsnot grpmax-eligible	0.0512%	1,953
Admixed American	0.0467%	2,143
Finnishnot grpmax-eligible	0.0406%	2,463
Middle Eastern	0.0165%	6,060
African / African-American	0.0107%	9,381
South Asian	0.00329%	30,361

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala173=
Coding: c.519G>A
MANE Select: NM_001395517 · reported on NM_024664
dbSNP: rs200337358
Type: single nucleotide variant
Location: chr1:42457257 (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-ala173 (accessed [today's date]).

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