Is PPIB p.Ala19Val (c.56C>T) pathogenic?

PPIB p.Ala19Val (c.56C>T) is classified Likely benign in PPIB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-02). AlphaMissense: likely benign (0.0891); Ultra-rare (popmax 0.0107%, afr); Associated with Inborn genetic diseases.

What condition is associated with PPIB p.Ala19Val (c.56C>T)?

PPIB p.Ala19Val (c.56C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PPIB p.Ala19Val (c.56C>T) in the general population?

PPIB p.Ala19Val (c.56C>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about PPIB p.Ala19Val (c.56C>T)?

AlphaMissense predicts likely benign (score 0.0891) — an in-silico prediction, not a clinical call.

PPIB p.Ala19Val

c.56C>T · rs537654261 · VCV3217184

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0891 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0891	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -6.13	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 2	GERP -1.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 6,960 bp · p 0.77 · regional, not allelic
Overall
CADD	11.82	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 0.0107% African / African-American · 8/75,058 alleles

Filtering AF 0.00527% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000558% 9/1,613,560 alleles · ultra-rare exomes 3/1,461,210 · genomes 6/152,350 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,382
Remaining individualsnot grpmax-eligible	0.0016%	62,444

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: PPIB
Protein: p.Ala19Val
Coding: c.56C>T
MANE Select: NM_000942
dbSNP: rs537654261
Type: single nucleotide variant
Location: chr15:64162931 (GRCh38)
Gene constraint: LOEUF 1.104 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 91.98 · 8 PDB

Full PPIB 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

PPIB p.Ala19= Uncertain significance ★ same residue
PPIB p.Arg7Ser Uncertain significance ★★ ⚠ same condition
PPIB p.Asn75Ser Uncertain significance ★★ ⚠ same condition
PPIB p.Glu183Ala Uncertain significance ★★ ⚠ same condition
PPIB p.Gly39Trp Uncertain significance ★★ ⚠ same condition
PPIB p.Lys116Arg Uncertain significance ★★ ⚠ same condition
PPIB p.Lys45Arg Uncertain significance ★★ ⚠ same condition
PPIB p.Lys92Arg 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/ppib-p-ala19val (accessed [today's date]).

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