Is PC p.Lys1130Arg (c.3389A>G) pathogenic?

PC p.Lys1130Arg (c.3389A>G) is classified Likely benign in PC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely benign (0.0758); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PC p.Lys1130Arg (c.3389A>G)?

PC p.Lys1130Arg (c.3389A>G) is associated with Inborn genetic diseases (ClinVar).

How common is PC p.Lys1130Arg (c.3389A>G) in the general population?

PC p.Lys1130Arg (c.3389A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PC p.Lys1130Arg (c.3389A>G)?

AlphaMissense predicts likely benign (score 0.0758) — an in-silico prediction, not a clinical call.

PC p.Lys1130Arg

c.3389A>G · rs2495378659 · VCV2491850

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0758 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0758	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -7.91	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 0.46	GERP -2.1, phastCons 0.98
Regional constraint	o/e 1.07	unconstrained · MANE · 198 bp · p 0.48 · regional, not allelic
Overall
CADD	11.19	PHRED · no single calibrated threshold — expert panels disagree

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.Lys1130Arg
Coding: c.3389A>G
MANE Select: NM_001040716
dbSNP: rs2495378659
Type: single nucleotide variant
Location: chr11:66849047 (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 1130: a β-strand; the biotinyl-binding 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.Lys1130Asn Uncertain significance ★ ⚠ same residue
PC p.Lys1130= Likely benign ★ same residue
PC p.Lys1130fs Pathogenic/Likely pathogenic ★★ 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

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-lys1130arg (accessed [today's date]).

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