Is SCRIB p.Gln1163Glu (c.3487C>G) pathogenic?

SCRIB p.Gln1163Glu (c.3487C>G) is classified Benign in SCRIB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-20). AlphaMissense: likely benign (0.139); Low-frequency (popmax 1.85%, eas); Associated with SCRIB-related disorder.

What condition is associated with SCRIB p.Gln1163Glu (c.3487C>G)?

SCRIB p.Gln1163Glu (c.3487C>G) is associated with SCRIB-related disorder (ClinVar).

How common is SCRIB p.Gln1163Glu (c.3487C>G) in the general population?

SCRIB p.Gln1163Glu (c.3487C>G) is low-frequency (popmax 1.85%, eas) (gnomAD).

What do computational predictors say about SCRIB p.Gln1163Glu (c.3487C>G)?

AlphaMissense predicts likely benign (score 0.139) — an in-silico prediction, not a clinical call.

SCRIB p.Gln1163Glu

c.3487C>G · rs138257744 · VCV3037548

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.139 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.85%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

SCRIB-related disorder

Computational evidence

Protein change
AlphaMissense	0.139	likely benign
REVEL	0.178	moderately benign-leaning
SaProt	LLR -7.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 20 kb · p 9.1e-08 · regional, not allelic
Overall
CADD	23.8	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 1.85% East Asian · 829/44,818 alleles

Filtering AF 1.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.7%

Overall 0.0638% 1,022/1,602,466 alleles · low-frequency exomes 873/1,450,178 · genomes 149/152,288 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	1.85%	54
Remaining individualsnot grpmax-eligible	0.133%	750
South Asian	0.0803%	1,246
African / African-American	0.024%	4,168
Admixed American	0.02%	4,994
Middle Eastern	0.0166%	6,014
European (non-Finnish)	0.000509%	196,569

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.Gln1163Glu
Coding: c.3487C>G
MANE Select: NM_182706
dbSNP: rs138257744
Type: single nucleotide variant
Location: chr8:143803499 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB
Residue 1163: the pdz 4 domain; the 'interaction with arhgef7' region; the 'required for interaction with vim' region

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

Disease context

SCRIB-related disorder

Similar variants

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
SCRIB c.907-4C>T 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-gln1163glu (accessed [today's date]).

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