Is PPP5C p.Glu305= (c.915G>A) pathogenic?

PPP5C p.Glu305= (c.915G>A) is classified Likely benign in PPP5C (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-04-29). Rare (popmax 0.144%, nfe); Associated with PPP5C-related disorder.

What condition is associated with PPP5C p.Glu305= (c.915G>A)?

PPP5C p.Glu305= (c.915G>A) is associated with PPP5C-related disorder (ClinVar).

How common is PPP5C p.Glu305= (c.915G>A) in the general population?

PPP5C p.Glu305= (c.915G>A) is rare (popmax 0.144%, nfe) (gnomAD).

PPP5C p.Glu305=

c.915G>A · rs147006420 · VCV3037600

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.144%, nfe)

Conditions

PPP5C-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.5	GERP 0.12, phastCons 1
Overall
CADD	8.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.144% European (non-Finnish) · 1,695/1,180,056 alleles

Filtering AF 0.138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.136%

Overall 0.111% 1,796/1,614,272 alleles · rare exomes 1,697/1,461,884 · genomes 99/152,388 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.144%	696
Finnishnot grpmax-eligible	0.0656%	1,525
Remaining individualsnot grpmax-eligible	0.0464%	2,156
African / African-American	0.0333%	3,003
Admixed American	0.00666%	15,008
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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: PPP5C
Protein: p.Glu305=
Coding: c.915G>A
MANE Select: NM_006247
dbSNP: rs147006420
Type: single nucleotide variant
Location: chr19:46387103 (GRCh38)
Gene constraint: LOEUF 0.456 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 93.00 · 22 PDB
Residue 305: a β-strand; the 'catalytic' region

Full PPP5C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PPP5C-related disorder

Similar variants

PPP5C p.Ala153Gly Uncertain significance ★ ⚠ same condition
PPP5C p.Ala47Thr Uncertain significance ⚠ same condition
PPP5C p.Ser164= Likely benign same condition
PPP5C p.Arg16fs Uncertain significance same condition
PPP5C p.Ala115Thr Uncertain significance ★ ⚠ same type
PPP5C p.Ala325Val Uncertain significance ★ ⚠ same type
PPP5C p.Ala54Ser Uncertain significance ★ ⚠ same type
PPP5C p.Ala62Thr Uncertain significance ★ ⚠ same type

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/ppp5c-p-glu305 (accessed [today's date]).

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