Is PPCS p.Ala24= (c.72T>C) pathogenic?

PPCS p.Ala24= (c.72T>C) is classified Likely benign in PPCS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-27). Very rare (popmax 0.00184%, amr).

How common is PPCS p.Ala24= (c.72T>C) in the general population?

PPCS p.Ala24= (c.72T>C) is very rare (popmax 0.00184%, amr) (gnomAD).

PPCS p.Ala24=

c.72T>C · rs1209740267 · VCV1988211

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00184%, amr)

⚠ 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 2.5	GERP 0.99, phastCons 1
Overall
CADD	14.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00184% Admixed American · 1/54,494 alleles

Overall 0.000127% 2/1,574,402 alleles · very rare exomes 1/1,422,214 · genomes 1/152,188 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00184%	54,494
European (non-Finnish)	8.59e-05%	1,164,086

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.Ala24=
Coding: c.72T>C
MANE Select: NM_024664
dbSNP: rs1209740267
Type: single nucleotide variant
Location: chr1:42456637 (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-ala24 (accessed [today's date]).

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