Is PLCD1 p.Arg60Trp (c.178C>T) pathogenic?

PLCD1 p.Arg60Trp (c.178C>T) is classified Uncertain significance in PLCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-07). AlphaMissense: ambiguous (0.41); Very rare (popmax 0.00831%, nfe).

How common is PLCD1 p.Arg60Trp (c.178C>T) in the general population?

PLCD1 p.Arg60Trp (c.178C>T) is very rare (popmax 0.00831%, nfe) (gnomAD).

What do computational predictors say about PLCD1 p.Arg60Trp (c.178C>T)?

AlphaMissense predicts ambiguous (score 0.41) — an in-silico prediction, not a clinical call.

PLCD1 p.Arg60Trp

c.178C>T · rs563968194 · VCV2455299

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.41 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00831%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.41	ambiguous
REVEL	0.245	benign-leaning
SaProt	LLR -10.70	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 22 kb · p 2.1e-05 · regional, not allelic
Overall
CADD	24.6	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 0.00831% European (non-Finnish) · 98/1,179,966 alleles

Filtering AF 0.00697% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00651% 105/1,613,772 alleles · very rare exomes 96/1,461,640 · genomes 9/152,132 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00831%	12,040
Remaining individualsnot grpmax-eligible	0.0064%	15,620
Admixed American	0.00333%	30,003
East Asian	0.00223%	44,882

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.Arg60Trp
Coding: c.178C>T
MANE Select: NM_006225
dbSNP: rs563968194
Type: single nucleotide variant
Location: chr3:38020209 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.31
Residue 60: the ph domain

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

Similar variants

PLCD1 p.Arg60Gln Uncertain significance ★★ ⚠ same residue
PLCD1 p.Arg530Ter Pathogenic/Likely pathogenic ★★ same type
PLCD1 p.Arg138His Uncertain significance ★★ ⚠ same type
PLCD1 p.Arg476His 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-arg60trp (accessed [today's date]).

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