Is PDE8A p.Val362Ile (c.1084G>A) pathogenic?

PDE8A p.Val362Ile (c.1084G>A) is classified Uncertain significance in PDE8A (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: likely benign (0.0729); Ultra-rare (popmax 0.0143%, sas).

How common is PDE8A p.Val362Ile (c.1084G>A) in the general population?

PDE8A p.Val362Ile (c.1084G>A) is ultra-rare (popmax 0.0143%, sas) (gnomAD).

What do computational predictors say about PDE8A p.Val362Ile (c.1084G>A)?

AlphaMissense predicts likely benign (score 0.0729) — an in-silico prediction, not a clinical call.

PDE8A p.Val362Ile

c.1084G>A · rs753388144 · VCV2293479

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0729 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0729	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -6.46	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 -0.049	GERP -3.3
Regional constraint	o/e 0.97	unconstrained · MANE · 156 kb · p 0.32 · regional, not allelic
Overall
CADD	14.31	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 0.0143% South Asian · 13/90,758 alleles

Filtering AF 0.00847% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00663%

Overall 0.0023% 37/1,611,626 alleles · ultra-rare exomes 36/1,459,466 · genomes 1/152,160 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0143%	6,981
Admixed American	0.00667%	14,985
African / African-American	0.00401%	24,958
East Asian	0.00223%	44,870
Remaining individualsnot grpmax-eligible	0.0016%	62,390
European (non-Finnish)	0.00127%	78,553

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: PDE8A
Protein: p.Val362Ile
Coding: c.1084G>A
MANE Select: NM_002605
dbSNP: rs753388144
Type: single nucleotide variant
Location: chr15:85109100 (GRCh38)
Gene constraint: LOEUF 0.631 · pLI 0.03 (gnomAD)
Structure: AlphaFold pLDDT 78.51 · 10 PDB

Full PDE8A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDE8A p.Val362Leu Uncertain significance ★ ⚠ same residue
PDE8A p.Ala366Val Uncertain significance ★ ⚠ same type
PDE8A p.Ala41Ser Uncertain significance ★ ⚠ same type
PDE8A p.Ala4Val Uncertain significance ★ ⚠ same type
PDE8A p.Ala630Val Uncertain significance ★ ⚠ same type
PDE8A p.Ala633Val Uncertain significance ★ ⚠ same type
PDE8A p.Ala667Thr Uncertain significance ★ ⚠ same type
PDE8A p.Ala792Gly 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/pde8a-p-val362ile (accessed [today's date]).

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