Is PROC p.Asp401Asn (c.1201G>A) pathogenic?

PROC p.Asp401Asn (c.1201G>A) is classified Pathogenic/Likely pathogenic in PROC (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-17). AlphaMissense: likely pathogenic (0.9305); Very rare (popmax 0.00833%, amr); Associated with Inborn genetic diseases.

How common is PROC p.Asp401Asn (c.1201G>A) in the general population?

PROC p.Asp401Asn (c.1201G>A) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about PROC p.Asp401Asn (c.1201G>A)?

AlphaMissense predicts likely pathogenic (score 0.9305) — an in-silico prediction, not a clinical call.

PROC p.Asp401Asn

Q: What condition is associated with PROC p.Asp401Asn (c.1201G>A)?

PROC p.Asp401Asn (c.1201G>A) is associated with Inborn genetic diseases, thrombophilia due to protein C deficiency, autosomal dominant, thrombophilia due to protein C deficiency, autosomal recessive (ClinVar).

c.1201G>A · rs142742242 · VCV161334

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely pathogenic

0.9305 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9305	likely pathogenic ✓ concordant with ClinVar
REVEL	0.841	moderately pathogenic-leaning
SaProt	LLR -12.12	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 2.1, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 9,000 bp · p 3.6e-05 · regional, not allelic
Overall
CADD	29.7	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 0.00833% Admixed American · 5/60,010 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00174% 28/1,613,040 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,002
European (non-Finnish)	0.00178%	56,186
Finnishnot grpmax-eligible	0.00158%	63,120
South Asian	0.0011%	91,088

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.Asp401Asn
Coding: c.1201G>A
MANE Select: NM_000312
dbSNP: rs142742242
Type: single nucleotide variant
Location: chr2:127428761 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.35 · 12 PDB
Residue 401: a UniProt-annotated variant site (in thph3; la jolla-2/osaka-7 and -8); a turn; a disulfide bond; the peptidase s1 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

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

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-asp401asn (accessed [today's date]).

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