Is PC p.Arg830His (c.2489G>A) pathogenic?

PC p.Arg830His (c.2489G>A) is classified Conflicting classifications of pathogenicity in PC (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-05-27). AlphaMissense: likely benign (0.0786); Ultra-rare (popmax 0.0367%, amr); Associated with Inborn genetic diseases.

What condition is associated with PC p.Arg830His (c.2489G>A)?

PC p.Arg830His (c.2489G>A) is associated with Inborn genetic diseases, pyruvate carboxylase deficiency disease (ClinVar).

How common is PC p.Arg830His (c.2489G>A) in the general population?

PC p.Arg830His (c.2489G>A) is ultra-rare (popmax 0.0367%, amr) (gnomAD).

What do computational predictors say about PC p.Arg830His (c.2489G>A)?

AlphaMissense predicts likely benign (score 0.0786) — an in-silico prediction, not a clinical call.

PC p.Arg830His

c.2489G>A · rs773519800 · VCV618261

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0786 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0367%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0786	likely benign
REVEL	0.388	indeterminate
SaProt	LLR -7.00	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 2, phastCons 0.77
Regional constraint	o/e 0.74	unconstrained · MANE · 23 kb · p 3.1e-25 · regional, not allelic
Overall
CADD	22.2	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

Grpmax group 0.0367% Admixed American · 22/60,010 alleles

Filtering AF 0.0248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0209%

Overall 0.00304% 49/1,613,812 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0367%	2,728
South Asian	0.0154%	6,506
Remaining individualsnot grpmax-eligible	0.0064%	15,620
African / African-American	0.00133%	74,908
European (non-Finnish)	0.000678%	147,504

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: PC
Protein: p.Arg830His
Coding: c.2489G>A
MANE Select: NM_001040716
dbSNP: rs773519800
Type: single nucleotide variant
Location: chr11:66850449 (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 830: 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

Also linked: pyruvate carboxylase deficiency disease

Similar variants

PC p.Arg830= Likely benign ★ same residue
PC c.1368+1G>A Likely pathogenic ★★ same condition
PC c.1826-1G>C Likely pathogenic ★★ same condition
PC c.1983-116C>T Likely pathogenic ★★ same condition
PC c.633+2T>C Likely pathogenic ★★ same condition
PC p.Ala610Thr Pathogenic ★★ same condition
PC p.Ala812Asp Likely pathogenic ★★ same condition
PC p.Arg18Ter Pathogenic/Likely pathogenic ★★ 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-arg830his (accessed [today's date]).

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