Is SCRIB p.Arg231Gln (c.692G>A) pathogenic?

SCRIB p.Arg231Gln (c.692G>A) is classified Uncertain significance in SCRIB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely benign (0.0978); Very rare (popmax 0.004%, afr); Associated with SCRIB-related disorder.

What condition is associated with SCRIB p.Arg231Gln (c.692G>A)?

SCRIB p.Arg231Gln (c.692G>A) is associated with SCRIB-related disorder (ClinVar).

How common is SCRIB p.Arg231Gln (c.692G>A) in the general population?

SCRIB p.Arg231Gln (c.692G>A) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about SCRIB p.Arg231Gln (c.692G>A)?

AlphaMissense predicts likely benign (score 0.0978) — an in-silico prediction, not a clinical call.

SCRIB p.Arg231Gln

c.692G>A · rs773718652 · VCV2628549

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0978 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

SCRIB-related disorder

Computational evidence

Protein change
AlphaMissense	0.0978	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -7.80	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 5.8	GERP 2, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 4,447 bp · p 0.0026 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.004% African / African-American · 3/74,944 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.00124% 20/1,612,180 alleles · very rare exomes 16/1,459,928 · genomes 4/152,252 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,981
Admixed American	0.00334%	29,982
Remaining individualsnot grpmax-eligible	0.0032%	31,228
East Asian	0.00223%	44,886
South Asian	0.0022%	45,528
European (non-Finnish)	0.000848%	117,990

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.Arg231Gln
Coding: c.692G>A
MANE Select: NM_182706
dbSNP: rs773718652
Type: single nucleotide variant
Location: chr8:143812912 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB
Residue 231: the 'sufficient for targeting to adherens junction and to inhibit cell proliferation' region

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

Disease context

SCRIB-related disorder

Similar variants

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
SCRIB p.Ala440Val 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-arg231gln (accessed [today's date]).

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