Is PLCD1 p.Pro417Arg (c.1250C>G) pathogenic?

PLCD1 p.Pro417Arg (c.1250C>G) is classified Uncertain significance in PLCD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-14). AlphaMissense: likely benign (0.2289); Ultra-rare (popmax 0.0901%, amr).

How common is PLCD1 p.Pro417Arg (c.1250C>G) in the general population?

PLCD1 p.Pro417Arg (c.1250C>G) is ultra-rare (popmax 0.0901%, amr) (gnomAD).

What do computational predictors say about PLCD1 p.Pro417Arg (c.1250C>G)?

AlphaMissense predicts likely benign (score 0.2289) — an in-silico prediction, not a clinical call.

PLCD1 p.Pro417Arg

c.1250C>G · rs200255245 · VCV2316709

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2289 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0901%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2289	likely benign
REVEL	0.426	indeterminate
SaProt	LLR -10.93	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.5	GERP -0.075, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 22 kb · p 2.1e-05 · regional, not allelic
Overall
CADD	20.8	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 0.0901% Admixed American · 54/59,948 alleles

Filtering AF 0.0709% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.064%

Overall 0.0529% 853/1,612,910 alleles · ultra-rare exomes 770/1,460,690 · genomes 83/152,220 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0901%	1,110
European (non-Finnish)	0.0651%	1,536
Remaining individualsnot grpmax-eligible	0.0288%	3,467
Finnishnot grpmax-eligible	0.0141%	7,103
African / African-American	0.004%	24,974
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,548

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: PLCD1
Protein: p.Pro417Arg
Coding: c.1250C>G
MANE Select: NM_006225
dbSNP: rs200255245
Type: single nucleotide variant
Location: chr3:38009941 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.31
Residue 417: the pi-plc x-box domain

Full PLCD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PLCD1 p.Arg530Ter Pathogenic/Likely pathogenic ★★ same type
PLCD1 p.Arg138His Uncertain significance ★★ ⚠ same type
PLCD1 p.Arg476His Uncertain significance ★★ ⚠ same type
PLCD1 p.Arg60Gln Uncertain significance ★★ ⚠ same type
PLCD1 p.Ser650Ala Uncertain significance ★★ ⚠ same type
PLCD1 c.1607-42C>T Benign ★★ same type
PLCD1 c.1724-186C>G Benign ★★ same type
PLCD1 c.1724-32C>T Benign ★★ 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/plcd1-p-pro417arg (accessed [today's date]).

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