Is PPCS p.Ala179= (c.537G>A) pathogenic?

PPCS p.Ala179= (c.537G>A) is classified Benign/Likely benign in PPCS (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Rare (popmax 0.673%, afr).

How common is PPCS p.Ala179= (c.537G>A) in the general population?

PPCS p.Ala179= (c.537G>A) is rare (popmax 0.673%, afr) (gnomAD).

PPCS p.Ala179=

c.537G>A · rs115737664 · VCV1545608

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.673%, 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.
REVEL	0.053	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -0.09	GERP 0.49, phastCons 0.14
Overall
CADD	14.13	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.673% African / African-American · 505/75,028 alleles

Filtering AF 0.624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.605%

Overall 0.0403% 650/1,614,124 alleles · rare exomes 353/1,461,890 · genomes 297/152,234 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.673%	149
Admixed American	0.112%	896
Remaining individualsnot grpmax-eligible	0.0672%	1,488
Middle Eastern	0.033%	3,029
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
South Asian	0.00329%	30,360
European (non-Finnish)	0.00254%	39,334

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.Ala179=
Coding: c.537G>A
MANE Select: NM_024664
dbSNP: rs115737664
Type: single nucleotide variant
Location: chr1:42457275 (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-ala179 (accessed [today's date]).

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