Is PROC p.Phe10= (c.30C>T) pathogenic?

PROC p.Phe10= (c.30C>T) is classified Conflicting classifications of pathogenicity in PROC (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-04-01). Rare (popmax 0.576%, amr); Associated with thrombophilia due to protein C deficiency, autosomal recessive.

What condition is associated with PROC p.Phe10= (c.30C>T)?

PROC p.Phe10= (c.30C>T) is associated with thrombophilia due to protein C deficiency, autosomal recessive, thrombophilia due to protein C deficiency, autosomal dominant (ClinVar).

How common is PROC p.Phe10= (c.30C>T) in the general population?

PROC p.Phe10= (c.30C>T) is rare (popmax 0.576%, amr) (gnomAD).

PROC p.Phe10=

Q: How is Severe hereditary thrombophilia due to congenital protein C deficiency inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.30C>T · rs148490199 · VCV469121

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.576%, amr)

Conditions

thrombophilia due to protein C deficiency, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.67	GERP -0.91
Overall
CADD	8.151	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.576% Admixed American · 346/60,024 alleles

Filtering AF 0.526% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.507%

Overall 0.0253% 409/1,613,872 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.576%	173
African / African-American	0.0373%	2,680
Remaining individualsnot grpmax-eligible	0.0224%	4,462
South Asian	0.0022%	45,529
European (non-Finnish)	0.00161%	62,106

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: PROC
Protein: p.Phe10=
Coding: c.30C>T
MANE Select: NM_000312
dbSNP: rs148490199
Type: single nucleotide variant
Location: chr2:127419972 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.35 · 12 PDB

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

Disease context

thrombophilia due to protein C deficiency, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: thrombophilia due to protein C deficiency, autosomal dominant

For Severe hereditary thrombophilia due to congenital protein C deficiency (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Neonatal
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

PROC p.Ala309Thr Pathogenic/Likely pathogenic ★★ ⚠ same condition
PROC p.Arg199Ter Pathogenic ★★ same condition
PROC p.Arg211Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
PROC p.Arg211Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
PROC p.Arg220Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
PROC p.Arg220Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
PROC p.Arg271Trp Pathogenic/Likely pathogenic ★★ same condition
PROC p.Arg272Cys 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/proc-p-phe10 (accessed [today's date]).

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