Is PPIG p.His429Asp (c.1285C>G) pathogenic?

PPIG p.His429Asp (c.1285C>G) is classified Uncertain significance in PPIG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-03). AlphaMissense: likely benign (0.1728); Ultra-rare (popmax 0.0626%, eas).

How common is PPIG p.His429Asp (c.1285C>G) in the general population?

PPIG p.His429Asp (c.1285C>G) is ultra-rare (popmax 0.0626%, eas) (gnomAD).

What do computational predictors say about PPIG p.His429Asp (c.1285C>G)?

AlphaMissense predicts likely benign (score 0.1728) — an in-silico prediction, not a clinical call.

PPIG p.His429Asp

c.1285C>G · rs761984175 · VCV2537927

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1728 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0626%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1728	likely benign
REVEL	0.178	moderately benign-leaning
SaProt	LLR -5.73	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 6	GERP 0.86, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 4,277 bp · p 0.75 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0626% East Asian · 28/44,720 alleles

Filtering AF 0.0444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0383%

Overall 0.00193% 31/1,609,092 alleles · ultra-rare exomes 26/1,457,312 · genomes 5/151,780 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0626%	1,597
Remaining individualsnot grpmax-eligible	0.00161%	62,296
South Asian	0.00111%	89,742
European (non-Finnish)	8.48e-05%	1,178,574

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: PPIG
Protein: p.His429Asp
Coding: c.1285C>G
MANE Select: NM_004792
dbSNP: rs761984175
Type: single nucleotide variant
Location: chr2:169636543 (GRCh38)
Gene constraint: LOEUF 0.472 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 56.64 · 4 PDB
Residue 429: the 'disordered' region

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

Similar variants

PPIG c.929+11A>G Benign ★★ same type
PPIG p.Asn672= Benign ★★ same type
PPIG p.Glu495= Benign ★★ same type
PPIG p.Thr54= Benign ★★ same type
PPIG p.Ala542Thr Uncertain significance ★ ⚠ same type
PPIG p.Arg235Gln Uncertain significance ★ ⚠ same type
PPIG p.Arg239Gln Uncertain significance ★ ⚠ same type
PPIG p.Arg350Lys 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/ppig-p-his429asp (accessed [today's date]).

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