Is PC p.Met801Thr (c.2402T>C) pathogenic?

PC p.Met801Thr (c.2402T>C) is classified Uncertain significance in PC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-04). AlphaMissense: likely pathogenic (0.8451); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PC p.Met801Thr (c.2402T>C)?

PC p.Met801Thr (c.2402T>C) is associated with Inborn genetic diseases (ClinVar).

How common is PC p.Met801Thr (c.2402T>C) in the general population?

PC p.Met801Thr (c.2402T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PC p.Met801Thr (c.2402T>C)?

AlphaMissense predicts likely pathogenic (score 0.8451) — an in-silico prediction, not a clinical call.

PC p.Met801Thr

c.2402T>C · rs1308988621 · VCV3209058

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8451 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8451	likely pathogenic
REVEL	0.944	strongly pathogenic-leaning
SaProt	LLR -11.92	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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 0.74	unconstrained · MANE · 23 kb · p 3.1e-25 · regional, not allelic
Overall
CADD	24.9	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: PC
Protein: p.Met801Thr
Coding: c.2402T>C
MANE Select: NM_001040716
dbSNP: rs1308988621
Type: single nucleotide variant
Location: chr11:66850745 (GRCh38)
Gene constraint: LOEUF 0.539 · pLI 0.07 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 90.53 · 10 PDB
Residue 801: an α-helix; the pyruvate carboxyltransferase domain

Full PC 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

PC p.Met801Leu Uncertain significance ★★ ⚠ same residue
PC p.Ala280Thr Uncertain significance ★★ ⚠ same condition
PC p.Ala431Gly Uncertain significance ★★ ⚠ same condition
PC p.Arg31His Uncertain significance ★★ ⚠ same condition
PC p.Arg385Cys Uncertain significance ★★ ⚠ same condition
PC p.Arg393Cys Uncertain significance ★★ ⚠ same condition
PC p.Arg77Trp Uncertain significance ★★ ⚠ same condition
PC p.Asp1067Asn 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/pc-p-met801thr (accessed [today's date]).

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