Is PCID2 p.Ser243Cys (c.728C>G) pathogenic?

PCID2 p.Ser243Cys (c.728C>G) is classified Uncertain significance in PCID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: likely benign (0.0971); Very rare (popmax 0.00167%, amr).

How common is PCID2 p.Ser243Cys (c.728C>G) in the general population?

PCID2 p.Ser243Cys (c.728C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about PCID2 p.Ser243Cys (c.728C>G)?

AlphaMissense predicts likely benign (score 0.0971) — an in-silico prediction, not a clinical call.

PCID2 p.Ser243Cys

c.728C>G · rs1182774429 · VCV2557882

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0971 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0971	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -9.93	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 2.1	GERP -3.2, phastCons 0.031
Regional constraint	o/e 0.76	unconstrained · MANE · 7,354 bp · p 4.2e-05 · regional, not allelic
Overall
CADD	18.81	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 0.00167% Admixed American · 1/59,992 alleles

Overall 0.000124% 2/1,613,704 alleles · very rare exomes 1/1,461,546 · genomes 1/152,158 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,992
African / African-American	0.00134%	74,886

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: PCID2
Protein: p.Ser243Cys
Coding: c.728C>G
MANE Select: NM_001127202
dbSNP: rs1182774429
Type: single nucleotide variant
Location: chr13:113181188 (GRCh38)
Gene constraint: LOEUF 1.174 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64 · 15 PDB
Residue 243: the pci domain

Full PCID2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PCID2 p.Gly135= Benign ★★ same type
PROZ p.Leu291Phe Benign ★★ same type
PROZ p.Thr316= Benign ★★ same type
PCID2 p.Ala297Val Uncertain significance ★ ⚠ same type
PCID2 p.Ala299Val Uncertain significance ★ ⚠ same type
PCID2 p.Ala37Val Uncertain significance ★ ⚠ same type
PCID2 p.Ala94Thr Uncertain significance ★ same type
PCID2 p.Arg116Gln Uncertain significance ★ ⚠ 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/pcid2-p-ser243cys (accessed [today's date]).

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