Is PLD1 p.Arg90His (c.269G>A) pathogenic?

PLD1 p.Arg90His (c.269G>A) is classified Benign in PLD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-09). AlphaMissense: likely benign (0.2422); Rare (popmax 0.696%, eas).

How common is PLD1 p.Arg90His (c.269G>A) in the general population?

PLD1 p.Arg90His (c.269G>A) is rare (popmax 0.696%, eas) (gnomAD).

What do computational predictors say about PLD1 p.Arg90His (c.269G>A)?

AlphaMissense predicts likely benign (score 0.2422) — an in-silico prediction, not a clinical call.

PLD1 p.Arg90His

c.269G>A · rs149506327 · VCV1587382

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2422 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.696%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2422	likely benign
REVEL	0.472	indeterminate
SaProt	LLR -6.39	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 135 kb · p 0.57 · regional, not allelic
Overall
CADD	29.7	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 0.696% East Asian · 312/44,858 alleles

Filtering AF 0.632% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.607%

Overall 0.0421% 678/1,610,666 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.696%	144
African / African-American	0.242%	413
South Asian	0.109%	919
Remaining individualsnot grpmax-eligible	0.0689%	1,450
Admixed American	0.0558%	1,793
Middle Eastern	0.0331%	3,021
European (non-Finnish)	0.000763%	131,020

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.Arg90His
Coding: c.269G>A
MANE Select: NM_002662
dbSNP: rs149506327
Type: single nucleotide variant
Location: chr3:171737551 (GRCh38)
Gene constraint: LOEUF 0.822 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.92 · 2 PDB
Residue 90: the px domain

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

Similar variants

PLD1 p.Arg90Cys Uncertain significance ★ ⚠ same residue
PLD1 c.2430-1G>A Pathogenic/Likely pathogenic ★★ same type
PLD1 c.2593+1G>A Pathogenic/Likely pathogenic ★★ same type
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

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-arg90his (accessed [today's date]).

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