Is SCRIB p.Ser504= (c.1512G>A) pathogenic?

SCRIB p.Ser504= (c.1512G>A) is classified Benign in SCRIB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-26). Common (popmax 8.79%, amr) — too common for a highly-penetrant pathogenic allele; Associated with SCRIB-related disorder.

What condition is associated with SCRIB p.Ser504= (c.1512G>A)?

SCRIB p.Ser504= (c.1512G>A) is associated with SCRIB-related disorder (ClinVar).

SCRIB p.Ser504=

Q: How common is SCRIB p.Ser504= (c.1512G>A) in the general population?

SCRIB p.Ser504= (c.1512G>A) is common (popmax 8.79%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1512G>A · rs144626855 · VCV3055855

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 8.79%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

SCRIB-related disorder

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 -7.6	GERP -2.9
Overall
CADD	0.217	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.79% Admixed American · 5,275/60,018 alleles

Filtering AF 8.59% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.51%

Overall 0.373% 6,003/1,610,122 alleles · common exomes 4,969/1,457,832 · genomes 1,034/152,290 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	8.79%	11
South Asian	0.322%	311
Remaining individualsnot grpmax-eligible	0.272%	367
East Asian	0.176%	568
African / African-American	0.128%	782
Middle Eastern	0.0675%	1,481
European (non-Finnish)	0.00729%	13,719

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.Ser504=
Coding: c.1512G>A
MANE Select: NM_182706
dbSNP: rs144626855
Type: single nucleotide variant
Location: chr8:143810497 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB
Residue 504: the 'sufficient for targeting to adherens junction and to inhibit cell proliferation' region; the 'disordered' region; a modified residue (phosphoserine)

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

Disease context

SCRIB-related disorder

Similar variants

SCRIB p.Ser504Leu Uncertain significance ★ ⚠ same residue
SCRIB p.Arg231Gln Uncertain significance ★ ⚠ same condition
SCRIB c.2179-10C>T Likely benign same condition
SCRIB c.3714+7G>A Likely benign same condition
SCRIB c.4018-6C>T Likely benign same condition
SCRIB c.4514+8C>T Likely benign same condition
SCRIB c.4515-4G>A Likely benign same condition
SCRIB c.907-4C>G Likely benign 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/scrib-p-ser504 (accessed [today's date]).

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