Is PROS1 p.Ser324Pro (c.970T>C) pathogenic?

PROS1 p.Ser324Pro (c.970T>C) is classified Likely pathogenic in PROS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-02-01). AlphaMissense: likely pathogenic (0.8252); Absent from gnomAD v4.1; Associated with protein S deficiency.

What condition is associated with PROS1 p.Ser324Pro (c.970T>C)?

PROS1 p.Ser324Pro (c.970T>C) is associated with protein S deficiency (ClinVar).

How common is PROS1 p.Ser324Pro (c.970T>C) in the general population?

PROS1 p.Ser324Pro (c.970T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PROS1 p.Ser324Pro (c.970T>C)?

AlphaMissense predicts likely pathogenic (score 0.8252) — an in-silico prediction, not a clinical call.

PROS1 p.Ser324Pro

c.970T>C · rs1576180280 · VCV627164

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8252 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

protein S deficiency

Computational evidence

Protein change
AlphaMissense	0.8252	likely pathogenic ✓ concordant with ClinVar
REVEL	0.659	pathogenic-leaning
SaProt	LLR -13.47	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 7.8	GERP 0.091, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 100 kb · p 4.7e-06 · regional, not allelic
Overall
CADD	24.4	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: PROS1
Protein: p.Ser324Pro
Coding: c.970T>C
MANE Select: NM_000313
dbSNP: rs1576180280
Type: single nucleotide variant
Location: chr3:93893118 (GRCh38)
Gene constraint: LOEUF 0.53 · pLI 0.75 (gnomAD)
Structure: AlphaFold pLDDT 83.06 · 3 PDB
Residue 324: the laminin g-like 1 domain; a UniProt-annotated variant site (in thph5)

Full PROS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

protein S deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PROS1 c.1155+5G>A Pathogenic/Likely pathogenic ★★ same condition
PROS1 c.-168C>T Likely pathogenic ★★ same condition
PROS1 p.Arg451Ter Pathogenic/Likely pathogenic ★★ same condition
PROS1 p.Cys639Tyr Pathogenic/Likely pathogenic ★★ same condition
PROS1 p.Cys666Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
PROS1 p.Tyr560Ter Pathogenic/Likely pathogenic ★★ same condition
PROS1 p.Arg330Trp Uncertain significance ★★ ⚠ same condition
PROS1 p.Thr518Met 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/pros1-p-ser324pro (accessed [today's date]).

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