Is PCID2 p.Ser198Pro (c.592T>C) pathogenic?

PCID2 p.Ser198Pro (c.592T>C) is classified Uncertain significance in PCID2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-10). AlphaMissense: likely pathogenic (0.9495); Absent from gnomAD v4.1.

How common is PCID2 p.Ser198Pro (c.592T>C) in the general population?

PCID2 p.Ser198Pro (c.592T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PCID2 p.Ser198Pro (c.592T>C)?

AlphaMissense predicts likely pathogenic (score 0.9495) — an in-silico prediction, not a clinical call.

PCID2 p.Ser198Pro

c.592T>C · VCV4133109

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9495 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9495	likely pathogenic
REVEL	0.358	indeterminate
SaProt	LLR -14.97	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 7,354 bp · p 4.2e-05 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PCID2
Protein: p.Ser198Pro
Coding: c.592T>C
MANE Select: NM_001127202
Type: single nucleotide variant
Location: chr13:113184439 (GRCh38)
Gene constraint: LOEUF 1.174 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.64 · 15 PDB

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

Similar variants

PROZ p.Glu198Lys Uncertain significance ★ ⚠ same residue
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

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-ser198pro (accessed [today's date]).

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