Is PLCD1 p.His291Pro (c.872A>C) pathogenic?

PLCD1 p.His291Pro (c.872A>C) is classified Uncertain significance in PLCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-17). AlphaMissense: ambiguous (0.4865); Ultra-rare (popmax 0.0165%, mid).

How common is PLCD1 p.His291Pro (c.872A>C) in the general population?

PLCD1 p.His291Pro (c.872A>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about PLCD1 p.His291Pro (c.872A>C)?

AlphaMissense predicts ambiguous (score 0.4865) — an in-silico prediction, not a clinical call.

PLCD1 p.His291Pro

c.872A>C · rs1197898815 · VCV3214437

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4865 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Computational evidence

Protein change
AlphaMissense	0.4865	ambiguous
REVEL	0.502	indeterminate
SaProt	LLR -12.18	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.1, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 22 kb · p 2.1e-05 · regional, not allelic
Overall
CADD	23.3	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 0.0165% Middle Eastern · 1/6,056 alleles

Filtering AF 0.00931% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00874%

Overall 0.00882% 142/1,609,614 alleles · ultra-rare exomes 142/1,457,376 · genomes 0/152,238 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,056
Remaining individualsnot grpmax-eligible	0.0112%	8,903
European (non-Finnish)	0.0109%	9,187
African / African-American	0.004%	24,989
South Asian	0.0033%	30,333

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.His291Pro
Coding: c.872A>C
MANE Select: NM_006225
dbSNP: rs1197898815
Type: single nucleotide variant
Location: chr3:38010481 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.31

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.Pro417Arg 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

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-his291pro (accessed [today's date]).

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