Is SCTR p.Pro415= (c.1245C>T) pathogenic?

SCTR p.Pro415= (c.1245C>T) is classified Benign in SCTR (ClinVar, Multiple submitters, 2 submitters; last evaluated 2017-08-11). Common (popmax 5.61%, afr) — too common for a highly-penetrant pathogenic allele.

SCTR p.Pro415=

Q: How common is SCTR p.Pro415= (c.1245C>T) in the general population?

SCTR p.Pro415= (c.1245C>T) is common (popmax 5.61%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1245C>T · rs75716989 · VCV785976

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.61%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.4	GERP -3.4
Overall
CADD	0.298	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.61% African / African-American · 4,207/75,044 alleles

Filtering AF 5.46% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.41%

Overall 0.305% 4,915/1,614,002 alleles · common exomes 2,462/1,461,678 · genomes 2,453/152,324 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.61%	18
Remaining individualsnot grpmax-eligible	0.472%	212
Admixed American	0.418%	239
Middle Eastern	0.317%	316
East Asian	0.0201%	4,985
South Asian	0.0143%	7,006
European (non-Finnish)	0.0103%	9,752

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: SCTR
Protein: p.Pro415=
Coding: c.1245C>T
MANE Select: NM_002980
dbSNP: rs75716989
Type: single nucleotide variant
Location: chr2:119440195 (GRCh38)
Gene constraint: LOEUF 1.373 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.18 · 3 PDB

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

Similar variants

SCTR c.851+10C>T Benign ★★ same type
SCTR p.Ala292Thr Likely benign ★★ same type
SCTR p.Asp110Asn Benign ★★ same type
SCTR p.Cys208= Benign ★★ same type
SCTR p.Leu190= Benign ★★ same type
SCTR p.Ala245Thr Uncertain significance ★ ⚠ same type
SCTR p.Ala375Val Uncertain significance ★ ⚠ same type
SCTR p.Arg135Gln Uncertain significance ★ ⚠ same type

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/sctr-p-pro415 (accessed [today's date]).

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