Is PPP1CA p.Pro115Arg (c.344C>G) pathogenic?

PPP1CA p.Pro115Arg (c.344C>G) is classified Uncertain significance in PPP1CA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-20). AlphaMissense: likely pathogenic (0.6819); Very rare (popmax 0.00267%, afr).

How common is PPP1CA p.Pro115Arg (c.344C>G) in the general population?

PPP1CA p.Pro115Arg (c.344C>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about PPP1CA p.Pro115Arg (c.344C>G)?

AlphaMissense predicts likely pathogenic (score 0.6819) — an in-silico prediction, not a clinical call.

PPP1CA p.Pro115Arg

c.344C>G · rs1244315422 · VCV2527366

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6819 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6819	likely pathogenic
REVEL	0.595	indeterminate
SaProt	LLR -9.64	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 2,460 bp · p 8.2e-21 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,942 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,978 alleles · very rare exomes 1/1,461,756 · genomes 1/152,222 · joint denominator

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: PPP1CA
Protein: p.Pro115Arg
Coding: c.344C>G
MANE Select: NM_002708
dbSNP: rs1244315422
Type: single nucleotide variant
Location: chr11:67400763 (GRCh38)
Gene constraint: LOEUF 0.554 · pLI 0.86 (gnomAD)
Structure: AlphaFold pLDDT 91.65 · 46 PDB
Residue 115: a turn

Full PPP1CA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PPP1CA c.56-31T>C Uncertain significance ★ same type
PPP1CA p.Ala326Thr Uncertain significance ★ ⚠ same type
PPP1CA p.Arg187Trp Uncertain significance ★ ⚠ same type
PPP1CA p.Arg261Gln Uncertain significance ★ ⚠ same type
PPP1CA p.Arg323Cys Uncertain significance ★ ⚠ same type
PPP1CA p.Arg323His Uncertain significance ★ ⚠ same type
PPP1CA p.Asn145Ser Uncertain significance ★ ⚠ same type
PPP1CA p.Asn278Ser 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/ppp1ca-p-pro115arg (accessed [today's date]).

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