Is PPA2 p.Ala264Val (c.791C>T) pathogenic?

PPA2 p.Ala264Val (c.791C>T) is classified Uncertain significance in PPA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-19). AlphaMissense: ambiguous (0.51); No allele count reported in gnomAD v4.1 (AN 1,589,228); Associated with sudden cardiac failure, infantile.

What condition is associated with PPA2 p.Ala264Val (c.791C>T)?

PPA2 p.Ala264Val (c.791C>T) is associated with sudden cardiac failure, infantile (ClinVar).

How common is PPA2 p.Ala264Val (c.791C>T) in the general population?

PPA2 p.Ala264Val (c.791C>T) is no allele count reported in gnomAD v4.1 (AN 1,589,228) (gnomAD).

What do computational predictors say about PPA2 p.Ala264Val (c.791C>T)?

AlphaMissense predicts ambiguous (score 0.51) — an in-silico prediction, not a clinical call.

PPA2 p.Ala264Val

c.791C>T · rs2110390901 · VCV1699311

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.51 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,589,228)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

sudden cardiac failure, infantile

Computational evidence

Protein change
AlphaMissense	0.51	ambiguous
REVEL	0.793	moderately pathogenic-leaning
SaProt	LLR -11.45	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 104 kb · p 0.35 · regional, not allelic
Overall
CADD	32.0	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

No allele count reported in gnomAD v4.1 (AN 1,589,228). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PPA2
Protein: p.Ala264Val
Coding: c.791C>T
MANE Select: NM_176869
dbSNP: rs2110390901
Type: single nucleotide variant
Location: chr4:105396327 (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

sudden cardiac failure, infantile — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PPA2 p.Arg127Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
PPA2 p.Glu172Lys Pathogenic/Likely pathogenic ★★ same condition
PPA2 p.Pro228Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
PPA2 p.Thr159Met Pathogenic/Likely pathogenic ★★ ⚠ same condition
PPA2 p.Ala130Val Uncertain significance ★★ ⚠ same condition
PPA2 c.442-16A>T Benign ★★ same condition
PPA2 p.Arg9= Benign/Likely benign ★★ same condition
PPA2 p.Lys282Asn Benign ★★ 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-ala264val (accessed [today's date]).

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