Is PLD1 p.Ile762Val (c.2284A>G) pathogenic?

PLD1 p.Ile762Val (c.2284A>G) is classified Uncertain significance in PLD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-22). AlphaMissense: likely benign (0.2794); Very rare (popmax 0.00267%, afr); Associated with cardiac valvular defect, developmental.

What condition is associated with PLD1 p.Ile762Val (c.2284A>G)?

PLD1 p.Ile762Val (c.2284A>G) is associated with cardiac valvular defect, developmental (ClinVar).

How common is PLD1 p.Ile762Val (c.2284A>G) in the general population?

PLD1 p.Ile762Val (c.2284A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about PLD1 p.Ile762Val (c.2284A>G)?

AlphaMissense predicts likely benign (score 0.2794) — an in-silico prediction, not a clinical call.

PLD1 p.Ile762Val

c.2284A>G · rs781545382 · VCV2434924

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2794 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cardiac valvular defect, developmental

Computational evidence

Protein change
AlphaMissense	0.2794	likely benign
REVEL	0.288	benign-leaning
SaProt	LLR -10.02	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 135 kb · p 0.57 · regional, not allelic
Overall
CADD	25.4	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 0.00267% African / African-American · 2/74,928 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.00131% 2/152,218 alleles · very rare

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: PLD1
Protein: p.Ile762Val
Coding: c.2284A>G
MANE Select: NM_002662
dbSNP: rs781545382
Type: single nucleotide variant
Location: chr3:171662116 (GRCh38)
Gene constraint: LOEUF 0.822 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.92 · 2 PDB
Residue 762: an α-helix; the 'catalytic' region

Full PLD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cardiac valvular defect, developmental — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PLD1 c.2593+1G>A Pathogenic/Likely pathogenic ★★ same condition
PLD1 p.Arg407Ter Pathogenic/Likely pathogenic ★★ same condition
PLD1 p.Arg298Gln Uncertain significance ★★ ⚠ same condition
PLD1 p.Arg440His Uncertain significance ★★ ⚠ same condition
PLD1 p.Asp661Val Uncertain significance ★★ ⚠ same condition
PLD1 p.Gly834Ser Uncertain significance ★★ ⚠ same condition
PLD1 p.Tyr894Cys Uncertain significance ★★ ⚠ same condition
PLD1 p.Ala622Ser 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/pld1-p-ile762val (accessed [today's date]).

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