Is PC p.Ile239Val (c.715A>G) pathogenic?

PC p.Ile239Val (c.715A>G) is classified Conflicting classifications of pathogenicity in PC (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.0821); Rare (popmax 0.105%, amr); Associated with Inborn genetic diseases.

What condition is associated with PC p.Ile239Val (c.715A>G)?

PC p.Ile239Val (c.715A>G) is associated with Inborn genetic diseases, pyruvate carboxylase deficiency disease (ClinVar).

How common is PC p.Ile239Val (c.715A>G) in the general population?

PC p.Ile239Val (c.715A>G) is rare (popmax 0.105%, amr) (gnomAD).

What do computational predictors say about PC p.Ile239Val (c.715A>G)?

AlphaMissense predicts likely benign (score 0.0821) — an in-silico prediction, not a clinical call.

PC p.Ile239Val

c.715A>G · rs148805312 · VCV305632

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0821 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.105%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0821	likely benign
REVEL	0.535	indeterminate
SaProt	LLR -7.53	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 5	GERP 2, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 23 kb · p 3.1e-25 · regional, not allelic
Overall
CADD	15.9	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 0.105% Admixed American · 63/60,032 alleles

Filtering AF 0.0841% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0766%

Overall 0.0222% 359/1,613,638 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.105%	953
Remaining individualsnot grpmax-eligible	0.0304%	3,289
European (non-Finnish)	0.0227%	4,403
African / African-American	0.0107%	9,380
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600

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.Ile239Val
Coding: c.715A>G
MANE Select: NM_001040716
dbSNP: rs148805312
Type: single nucleotide variant
Location: chr11:66870811 (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 239: the biotin carboxylation domain; the atp-grasp 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.Ile239= 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-ile239val (accessed [today's date]).

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