Is PPP3CA p.Ala31Ser (c.91G>T) pathogenic?

PPP3CA p.Ala31Ser (c.91G>T) is classified Likely benign in PPP3CA (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.0704); Rare (popmax 0.66%, mid); Associated with Inborn genetic diseases.

What condition is associated with PPP3CA p.Ala31Ser (c.91G>T)?

PPP3CA p.Ala31Ser (c.91G>T) is associated with Inborn genetic diseases (ClinVar).

How common is PPP3CA p.Ala31Ser (c.91G>T) in the general population?

PPP3CA p.Ala31Ser (c.91G>T) is rare (popmax 0.66%, mid) (gnomAD).

What do computational predictors say about PPP3CA p.Ala31Ser (c.91G>T)?

AlphaMissense predicts likely benign (score 0.0704) — an in-silico prediction, not a clinical call.

PPP3CA p.Ala31Ser

c.91G>T · rs200056844 · VCV1205977

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0704 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.66%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0704	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 151 kb · p 0.018 · regional, not allelic
Overall
CADD	22.5	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 0.66% Middle Eastern · 40/6,060 alleles

Filtering AF 0.498% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.442%

Overall 0.032% 516/1,613,910 alleles · rare exomes 429/1,461,684 · genomes 87/152,226 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.66%	152
Admixed American	0.18%	555
Remaining individualsnot grpmax-eligible	0.11%	906
African / African-American	0.036%	2,778
European (non-Finnish)	0.0231%	4,338

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: PPP3CA
Protein: p.Ala31Ser
Coding: c.91G>T
MANE Select: NM_000944
dbSNP: rs200056844
Type: single nucleotide variant
Location: chr4:101196084 (GRCh38)
Gene constraint: LOEUF 0.243 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 86.24 · 21 PDB
Residue 31: an α-helix

Full PPP3CA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PPP3CA p.Ala31Thr Uncertain significance ★ ⚠ same residue
PPP3CA p.His92Arg Pathogenic/Likely pathogenic ★★ same condition
PPP3CA p.Ala83Val Uncertain significance ★★ ⚠ same condition
PPP3CA p.Asn37Lys Uncertain significance ★★ ⚠ same condition
PPP3CA p.Ile7Val Uncertain significance ★★ ⚠ same condition
PPP3CA p.Lys142Glu Uncertain significance ★★ ⚠ same condition
PPP3CA p.Lys405Arg Uncertain significance ★★ ⚠ same condition
PPP3CA p.Phe470Leu Uncertain significance ★★ ⚠ same condition

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/ppp3ca-p-ala31ser (accessed [today's date]).

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