Is PLCD1 p.Pro617Ser (c.1849C>T) pathogenic?

PLCD1 p.Pro617Ser (c.1849C>T) is classified Likely benign in PLCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-26). AlphaMissense: likely benign (0.2646); Ultra-rare (popmax 0.0317%, amr).

How common is PLCD1 p.Pro617Ser (c.1849C>T) in the general population?

PLCD1 p.Pro617Ser (c.1849C>T) is ultra-rare (popmax 0.0317%, amr) (gnomAD).

What do computational predictors say about PLCD1 p.Pro617Ser (c.1849C>T)?

AlphaMissense predicts likely benign (score 0.2646) — an in-silico prediction, not a clinical call.

PLCD1 p.Pro617Ser

c.1849C>T · rs769126654 · VCV2370884

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2646 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0317%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2646	likely benign
REVEL	0.282	benign-leaning
SaProt	LLR -12.93	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.22	GERP -4, phastCons 0.66
Regional constraint	o/e 0.87	unconstrained · MANE · 22 kb · p 2.1e-05 · regional, not allelic
Overall
CADD	4.57	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 0.0317% Admixed American · 19/60,012 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.00124% 20/1,614,090 alleles · ultra-rare exomes 18/1,461,864 · genomes 2/152,226 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0317%	3,159
European (non-Finnish)	8.47e-05%	1,180,036

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.Pro617Ser
Coding: c.1849C>T
MANE Select: NM_006225
dbSNP: rs769126654
Type: single nucleotide variant
Location: chr3:38008511 (GRCh38)
Gene constraint: LOEUF 0.954 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.31
Residue 617: the c2 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.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-pro617ser (accessed [today's date]).

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