Is PLD1 p.Val792Leu (c.2374G>C) pathogenic?

PLD1 p.Val792Leu (c.2374G>C) is classified Benign in PLD1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-08-03). AlphaMissense: likely benign (0.1205); Rare (popmax 0.788%, afr).

How common is PLD1 p.Val792Leu (c.2374G>C) in the general population?

PLD1 p.Val792Leu (c.2374G>C) is rare (popmax 0.788%, afr) (gnomAD).

What do computational predictors say about PLD1 p.Val792Leu (c.2374G>C)?

AlphaMissense predicts likely benign (score 0.1205) — an in-silico prediction, not a clinical call.

PLD1 p.Val792Leu

c.2374G>C · rs146759449 · VCV1600735

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1205 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.788%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1205	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -5.81	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 4.9	GERP 0.058, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 135 kb · p 0.57 · regional, not allelic
Overall
CADD	19.41	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 0.788% African / African-American · 591/75,038 alleles

Filtering AF 0.735% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.714%

Overall 0.0398% 643/1,613,572 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.788%	127
Middle Eastern	0.066%	1,516
Remaining individualsnot grpmax-eligible	0.0352%	2,840
Admixed American	0.035%	2,858
South Asian	0.0011%	91,076
European (non-Finnish)	0.000339%	294,871

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.Val792Leu
Coding: c.2374G>C
MANE Select: NM_002662
dbSNP: rs146759449
Type: single nucleotide variant
Location: chr3:171659268 (GRCh38)
Gene constraint: LOEUF 0.822 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.92 · 2 PDB
Residue 792: a β-strand; the 'catalytic' region

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

Similar variants

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PLD1 p.Arg407Ter Pathogenic/Likely pathogenic ★★ same type
PLD1 p.Tyr894Ser Likely pathogenic ★★ same type
PLD1 p.Ala689Val Uncertain significance ★★ ⚠ same type
PLD1 p.Ala765Thr Uncertain significance ★★ ⚠ same type
PLD1 p.Arg172Lys Uncertain significance ★★ ⚠ same type
PLD1 p.Arg298Gln 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/pld1-p-val792leu (accessed [today's date]).

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