Is PC p.Arg385Cys (c.1153C>T) pathogenic?

PC p.Arg385Cys (c.1153C>T) is classified Uncertain significance in PC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-09). AlphaMissense: likely benign (0.2982); Ultra-rare (popmax 0.03%, amr); Associated with Inborn genetic diseases.

What condition is associated with PC p.Arg385Cys (c.1153C>T)?

PC p.Arg385Cys (c.1153C>T) is associated with Inborn genetic diseases, pyruvate carboxylase deficiency disease (ClinVar).

How common is PC p.Arg385Cys (c.1153C>T) in the general population?

PC p.Arg385Cys (c.1153C>T) is ultra-rare (popmax 0.03%, amr) (gnomAD).

What do computational predictors say about PC p.Arg385Cys (c.1153C>T)?

AlphaMissense predicts likely benign (score 0.2982) — an in-silico prediction, not a clinical call.

PC p.Arg385Cys

c.1153C>T · rs773109008 · VCV1438119

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2982 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.03%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2982	likely benign
REVEL	0.765	pathogenic-leaning
SaProt	LLR -9.51	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 23 kb · p 3.1e-25 · regional, not allelic
Overall
CADD	33.0	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 0.03% Admixed American · 18/59,974 alleles

Filtering AF 0.0194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00168% 27/1,611,270 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.03%	3,332
South Asian	0.0022%	45,506
Remaining individualsnot grpmax-eligible	0.0016%	62,376
European (non-Finnish)	0.000509%	196,613

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.Arg385Cys
Coding: c.1153C>T
MANE Select: NM_001040716
dbSNP: rs773109008
Type: single nucleotide variant
Location: chr11:66866219 (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 385: the biotin carboxylation domain; a turn

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.Arg385= Likely benign ★ same residue
PC p.Arg385fs Likely pathogenic 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

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-arg385cys (accessed [today's date]).

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