Is PC p.Ser266Tyr (c.797C>A) pathogenic?

PC p.Ser266Tyr (c.797C>A) is classified Pathogenic in PC (ClinVar, Single submitter, 1 submitter; last evaluated 2012-11-27). AlphaMissense: likely pathogenic (0.997); No allele count reported in gnomAD v4.1 (AN 1,613,764).

How common is PC p.Ser266Tyr (c.797C>A) in the general population?

PC p.Ser266Tyr (c.797C>A) is no allele count reported in gnomAD v4.1 (AN 1,613,764) (gnomAD).

What do computational predictors say about PC p.Ser266Tyr (c.797C>A)?

AlphaMissense predicts likely pathogenic (score 0.997) — an in-silico prediction, not a clinical call.

PC p.Ser266Tyr

c.797C>A · rs796052030 · VCV203922

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.997 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,764)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.997	likely pathogenic ✓ concordant with ClinVar · top 4% in PC
REVEL	0.953	strongly pathogenic-leaning
SaProt	LLR -16.72	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, 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

No allele count reported in gnomAD v4.1 (AN 1,613,764). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PC
Protein: p.Ser266Tyr
Coding: c.797C>A
MANE Select: NM_001040716
dbSNP: rs796052030
Type: single nucleotide variant
Location: chr11:66870408 (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 266: the biotin carboxylation domain; the atp-grasp domain; a β-strand

Full PC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PC p.Ser266Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
PC c.1368+1G>A Likely pathogenic ★★ same type
PC c.1826-1G>C Likely pathogenic ★★ same type
PC c.1983-116C>T Likely pathogenic ★★ same type
PC c.633+2T>C Likely pathogenic ★★ same type
PC p.Ala610Thr Pathogenic ★★ same type
PC p.Ala812Asp Likely pathogenic ★★ same type
PC p.Arg18Ter Pathogenic/Likely pathogenic ★★ same type

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-ser266tyr (accessed [today's date]).

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