Is PLCE1 p.Ser900Phe (c.2699C>T) pathogenic?

PLCE1 p.Ser900Phe (c.2699C>T) is classified Uncertain significance in PLCE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-22). AlphaMissense: likely benign (0.0969); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with PLCE1 p.Ser900Phe (c.2699C>T)?

PLCE1 p.Ser900Phe (c.2699C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PLCE1 p.Ser900Phe (c.2699C>T) in the general population?

PLCE1 p.Ser900Phe (c.2699C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about PLCE1 p.Ser900Phe (c.2699C>T)?

AlphaMissense predicts likely benign (score 0.0969) — an in-silico prediction, not a clinical call.

PLCE1 p.Ser900Phe

c.2699C>T · rs1193228304 · VCV2621137

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0969 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0969	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -8.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 214 kb · p 0.44 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Overall 0.000248% 4/1,614,046 alleles · very rare exomes 3/1,461,846 · genomes 1/152,200 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,880
Remaining individualsnot grpmax-eligible	0.0016%	62,488
African / African-American	0.00133%	74,934
South Asian	0.0011%	91,082

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: PLCE1
Protein: p.Ser900Phe
Coding: c.2699C>T
MANE Select: NM_016341
dbSNP: rs1193228304
Type: single nucleotide variant
Location: chr10:94246224 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 61.01 · 3 PDB

Full PLCE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PLCE1 c.4917+3G>A Uncertain significance ★★ same condition
PLCE1 p.Arg1057Gln Uncertain significance ★★ ⚠ same condition
PLCE1 p.Arg1116Gln Uncertain significance ★★ ⚠ same condition
PLCE1 p.Arg1118Gln Uncertain significance ★★ ⚠ same condition
PLCE1 p.Arg1147Gly Uncertain significance ★★ ⚠ same condition
PLCE1 p.Arg693Cys Uncertain significance ★★ ⚠ same condition
PLCE1 p.Arg729Gln Uncertain significance ★★ ⚠ same condition
PLCE1 p.Arg775Trp Uncertain significance ★★ 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/plce1-p-ser900phe (accessed [today's date]).

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