Is PPIC p.Asn190Asp (c.568A>G) pathogenic?

PPIC p.Asn190Asp (c.568A>G) is classified Likely benign in PPIC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). AlphaMissense: likely benign (0.0602); Ultra-rare (popmax 0.0943%, nfe).

How common is PPIC p.Asn190Asp (c.568A>G) in the general population?

PPIC p.Asn190Asp (c.568A>G) is ultra-rare (popmax 0.0943%, nfe) (gnomAD).

What do computational predictors say about PPIC p.Asn190Asp (c.568A>G)?

AlphaMissense predicts likely benign (score 0.0602) — an in-silico prediction, not a clinical call.

PPIC p.Asn190Asp

c.568A>G · rs137956160 · VCV3217187

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0602 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0943%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0602	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -4.00	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 0.034	GERP -0.078, phastCons 0.002
Regional constraint	o/e 1.00	unconstrained · MANE · 13 kb · p 0.97 · regional, not allelic
Overall
CADD	11.3	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 0.0943% European (non-Finnish) · 1,113/1,180,010 alleles

Filtering AF 0.0897% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0878%

Overall 0.075% 1,211/1,614,054 alleles · ultra-rare exomes 1,117/1,461,854 · genomes 94/152,200 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0943%	1,060
Ashkenazi Jewishnot grpmax-eligible	0.0709%	1,410
Admixed American	0.0533%	1,875
Remaining individualsnot grpmax-eligible	0.0336%	2,977
Middle Eastern	0.033%	3,028
African / African-American	0.0213%	4,688
Finnishnot grpmax-eligible	0.00937%	10,670

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: PPIC
Protein: p.Asn190Asp
Coding: c.568A>G
MANE Select: NM_000943
dbSNP: rs137956160
Type: single nucleotide variant
Location: chr5:123023946 (GRCh38)
Gene constraint: LOEUF 1.354 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.88 · 1 PDB
Residue 190: the ppiase cyclophilin-type domain; a UniProt-annotated variant site (in)

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

Similar variants

PPIC p.Ala137Thr Uncertain significance ★ ⚠ same type
PPIC p.Ala19Val Uncertain significance ★ ⚠ same type
PPIC p.Ala210Thr Uncertain significance ★ ⚠ same type
PPIC p.Arg6Gln Uncertain significance ★ ⚠ same type
PPIC p.Asp185Glu Uncertain significance ★ ⚠ same type
PPIC p.Asp200Gly Uncertain significance ★ ⚠ same type
PPIC p.Glu115Asp Uncertain significance ★ ⚠ same type
PPIC p.Gly130Glu 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/ppic-p-asn190asp (accessed [today's date]).

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