Is PLCD1 p.Ser548= (c.1644C>T) pathogenic?

PLCD1 p.Ser548= (c.1644C>T) is classified Likely benign in PLCD1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-05). Ultra-rare (popmax 0.0617%, nfe); Associated with PLCD1-related disorder.

What condition is associated with PLCD1 p.Ser548= (c.1644C>T)?

PLCD1 p.Ser548= (c.1644C>T) is associated with PLCD1-related disorder (ClinVar).

How common is PLCD1 p.Ser548= (c.1644C>T) in the general population?

PLCD1 p.Ser548= (c.1644C>T) is ultra-rare (popmax 0.0617%, nfe) (gnomAD).

PLCD1 p.Ser548=

c.1644C>T · rs113896726 · VCV3044078

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0617%, nfe)

Conditions

PLCD1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.68, phastCons 1
Overall
CADD	12.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0617% European (non-Finnish) · 728/1,180,028 alleles

Filtering AF 0.0579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0564%

Overall 0.0502% 811/1,614,064 alleles · ultra-rare exomes 762/1,461,818 · genomes 49/152,246 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.08%	1,250
European (non-Finnish)grpmax	0.0617%	1,621
Admixed American	0.04%	2,501
African / African-American	0.0107%	9,368
Finnishnot grpmax-eligible	0.00156%	64,048

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser548=
Coding: c.1644C>T
MANE Select: NM_006225
dbSNP: rs113896726
Type: single nucleotide variant
Location: chr3:38009121 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.31
Residue 548: the pi-plc y-box domain

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

Disease context

PLCD1-related disorder

Similar variants

PLCD1 p.Ala553Thr Conflicting classifications of pathogenicity ⚠ same condition
PLCD1 p.Glu462Lys Uncertain significance ⚠ same condition
PLCD1 c.429-5C>T Likely benign same condition
PLCD1 c.993-4G>A Likely benign same condition
PLCD1 c.993-5C>T Likely benign same condition
PLCD1 p.Ala249= Likely benign same condition
PLCD1 p.His546= Likely benign same condition
PLCD1 p.Lys49= Likely 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/plcd1-p-ser548 (accessed [today's date]).

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