Is SCRIB p.Pro213Ser (c.637C>T) pathogenic?

SCRIB p.Pro213Ser (c.637C>T) is classified Uncertain significance in SCRIB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: likely pathogenic (0.9473); Very rare (popmax 0.00112%, sas).

How common is SCRIB p.Pro213Ser (c.637C>T) in the general population?

SCRIB p.Pro213Ser (c.637C>T) is very rare (popmax 0.00112%, sas) (gnomAD).

What do computational predictors say about SCRIB p.Pro213Ser (c.637C>T)?

AlphaMissense predicts likely pathogenic (score 0.9473) — an in-silico prediction, not a clinical call.

SCRIB p.Pro213Ser

c.637C>T · VCV4160857

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9473 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00112%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.9473	likely pathogenic
REVEL	0.409	indeterminate
SaProt	LLR -12.89	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 4,447 bp · p 0.0026 · regional, not allelic
Overall
CADD	27.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00112% South Asian · 1/89,300 alleles

Filtering AF 0.000125% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.1e-05%

Overall 0.000375% 6/1,599,588 alleles · very rare exomes 6/1,447,212 · genomes 0/152,376 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00112%	89,300
European (non-Finnish)	0.000426%	234,800

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: SCRIB
Protein: p.Pro213Ser
Coding: c.637C>T
MANE Select: NM_182706
Type: single nucleotide variant
Location: chr8:143813035 (GRCh38)

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

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/scrib-p-pro213ser (accessed [today's date]).

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