Is PPA2 p.Ile207Val (c.619A>G) pathogenic?

PPA2 p.Ile207Val (c.619A>G) is classified Uncertain significance in PPA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-10). AlphaMissense: likely benign (0.086); Very rare (popmax 0.00536%, afr); Associated with Inborn genetic diseases.

What condition is associated with PPA2 p.Ile207Val (c.619A>G)?

PPA2 p.Ile207Val (c.619A>G) is associated with Inborn genetic diseases (ClinVar).

How common is PPA2 p.Ile207Val (c.619A>G) in the general population?

PPA2 p.Ile207Val (c.619A>G) is very rare (popmax 0.00536%, afr) (gnomAD).

What do computational predictors say about PPA2 p.Ile207Val (c.619A>G)?

AlphaMissense predicts likely benign (score 0.086) — an in-silico prediction, not a clinical call.

PPA2 p.Ile207Val

c.619A>G · rs1486574937 · VCV2482770

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.086 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00536%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.086	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -9.10	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 104 kb · p 0.35 · regional, not allelic
Overall
CADD	24.5	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 0.00536% African / African-American · 4/74,680 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000311% 5/1,609,460 alleles · very rare exomes 3/1,457,268 · genomes 2/152,192 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00536%	18,670
South Asian	0.00111%	89,722

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: PPA2
Protein: p.Ile207Val
Coding: c.619A>G
MANE Select: NM_176869
dbSNP: rs1486574937
Type: single nucleotide variant
Location: chr4:105424232 (GRCh38)
Gene constraint: LOEUF 1.324 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.39

Full PPA2 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

PPA2 p.Ala12Val Uncertain significance ★★ ⚠ same condition
PPA2 p.Ala16Val Uncertain significance ★★ ⚠ same condition
PPA2 p.Arg9Leu Uncertain significance ★★ ⚠ same condition
PPA2 p.Asn260Ser Uncertain significance ★★ ⚠ same condition
PPA2 p.Asn319Tyr Uncertain significance ★★ ⚠ same condition
PPA2 p.Asp156Tyr Uncertain significance ★★ ⚠ same condition
PPA2 p.Asp245Asn Uncertain significance ★★ ⚠ same condition
PPA2 p.Gln251Leu 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/ppa2-p-ile207val (accessed [today's date]).

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