Is PROC p.Cys101Gly (c.301T>G) pathogenic?

PROC p.Cys101Gly (c.301T>G) is classified Uncertain significance in PROC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-08). AlphaMissense: ambiguous (0.4064); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PROC p.Cys101Gly (c.301T>G)?

PROC p.Cys101Gly (c.301T>G) is associated with Inborn genetic diseases (ClinVar).

How common is PROC p.Cys101Gly (c.301T>G) in the general population?

PROC p.Cys101Gly (c.301T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PROC p.Cys101Gly (c.301T>G)?

AlphaMissense predicts ambiguous (score 0.4064) — an in-silico prediction, not a clinical call.

PROC p.Cys101Gly

c.301T>G · rs2468336513 · VCV2617567

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4064 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4064	ambiguous
REVEL	0.632	indeterminate
SaProt	LLR -3.03	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 9,000 bp · p 3.6e-05 · regional, not allelic
Overall
CADD	24.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PROC
Protein: p.Cys101Gly
Coding: c.301T>G
MANE Select: NM_000312
dbSNP: rs2468336513
Type: single nucleotide variant
Location: chr2:127423072 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.35 · 12 PDB
Residue 101: a β-strand; a disulfide bond; the egf-like 1 domain

Full PROC 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

Similar variants

PROC p.Cys101Ter Conflicting classifications of pathogenicity ★ same residue
PROC p.Asp401Asn Pathogenic/Likely pathogenic ★★ same condition
PROC p.Val339Met Pathogenic ★★ same condition
PROC p.Trp414Arg Uncertain significance ★★ ⚠ same condition
PROC p.Arg189Gly Uncertain significance ★ ⚠ same condition
PROC p.Asn384Ser Uncertain significance ★ ⚠ same condition
PROC p.Asn431Ser Uncertain significance ★ ⚠ same condition
PROC p.Glu154Lys Uncertain significance ★ ⚠ 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/proc-p-cys101gly (accessed [today's date]).

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