Is PC p.Glu33Val (c.98A>T) pathogenic?

PC p.Glu33Val (c.98A>T) is classified Uncertain significance in PC (ClinVar, Single submitter, 1 submitter; last evaluated 2017-08-08). AlphaMissense: likely benign (0.1424); Absent from gnomAD v4.1.

How common is PC p.Glu33Val (c.98A>T) in the general population?

PC p.Glu33Val (c.98A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PC p.Glu33Val (c.98A>T)?

AlphaMissense predicts likely benign (score 0.1424) — an in-silico prediction, not a clinical call.

PC p.Glu33Val

c.98A>T · rs1555027633 · VCV451317

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1424 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1424	likely benign
REVEL	0.512	indeterminate
SaProt	LLR -6.95	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 23 kb · p 3.1e-25 · regional, not allelic
Overall
CADD	24.7	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

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: PC
Protein: p.Glu33Val
Coding: c.98A>T
MANE Select: NM_001040716
dbSNP: rs1555027633
Type: single nucleotide variant
Location: chr11:66872062 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI 0.07 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.53 · 10 PDB

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

Similar variants

PC c.1368+1G>A Likely pathogenic ★★ same type
PC c.1826-1G>C Likely pathogenic ★★ same type
PC c.1983-116C>T Likely pathogenic ★★ same type
PC c.633+2T>C Likely pathogenic ★★ same type
PC p.Ala610Thr Pathogenic ★★ same type
PC p.Ala812Asp Likely pathogenic ★★ same type
PC p.Arg18Ter Pathogenic/Likely pathogenic ★★ same type
PC p.Arg263Ter Pathogenic ★★ 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/pc-p-glu33val (accessed [today's date]).

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