Is PC p.Arg17His (c.50G>A) pathogenic?

PC p.Arg17His (c.50G>A) is classified Conflicting classifications of pathogenicity in PC (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-05-09). AlphaMissense: likely benign (0.1477); Ultra-rare (popmax 0.0146%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PC p.Arg17His (c.50G>A)?

PC p.Arg17His (c.50G>A) is associated with Inborn genetic diseases, pyruvate carboxylase deficiency disease (ClinVar).

How common is PC p.Arg17His (c.50G>A) in the general population?

PC p.Arg17His (c.50G>A) is ultra-rare (popmax 0.0146%, nfe) (gnomAD).

What do computational predictors say about PC p.Arg17His (c.50G>A)?

AlphaMissense predicts likely benign (score 0.1477) — an in-silico prediction, not a clinical call.

PC p.Arg17His

c.50G>A · rs375282341 · VCV203905

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1477 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0146%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1477	likely benign
REVEL	0.319	indeterminate
SaProt	LLR -10.27	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP -0.49, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 23 kb · p 3.1e-25 · regional, not allelic
Overall
CADD	22.3	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 0.0146% European (non-Finnish) · 170/1,161,102 alleles

Filtering AF 0.0128% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.0119% 188/1,575,030 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0146%	6,830
Admixed American	0.0129%	7,759
Remaining individualsnot grpmax-eligible	0.0115%	8,723
African / African-American	0.00406%	24,631
Finnishnot grpmax-eligible	0.00165%	60,764

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.Arg17His
Coding: c.50G>A
MANE Select: NM_001040716
dbSNP: rs375282341
Type: single nucleotide variant
Location: chr11:66872110 (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

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 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
PC p.Arg263Ter 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-arg17his (accessed [today's date]).

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