Is SCRIB p.Gly980Arg (c.2938G>A) pathogenic?

SCRIB p.Gly980Arg (c.2938G>A) is classified Benign in SCRIB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-06). AlphaMissense: likely benign (0.1516); Common (popmax 16.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with SCRIB-related disorder.

What condition is associated with SCRIB p.Gly980Arg (c.2938G>A)?

SCRIB p.Gly980Arg (c.2938G>A) is associated with SCRIB-related disorder (ClinVar).

What do computational predictors say about SCRIB p.Gly980Arg (c.2938G>A)?

AlphaMissense predicts likely benign (score 0.1516) — an in-silico prediction, not a clinical call.

SCRIB p.Gly980Arg

Q: How common is SCRIB p.Gly980Arg (c.2938G>A) in the general population?

SCRIB p.Gly980Arg (c.2938G>A) is common (popmax 16.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2938G>A · rs11542374 · VCV3060385

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1516 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 16.2%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

SCRIB-related disorder

Computational evidence

Protein change
AlphaMissense	0.1516	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2	GERP 0.013, phastCons 0.064
Regional constraint	o/e 1.13	unconstrained · MANE · 20 kb · p 9.1e-08 · regional, not allelic
Overall
CADD	17.22	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 16.2% African / African-American · 11,818/73,132 alleles

Filtering AF 15.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.8%

Overall 5.96% 91,673/1,537,270 alleles · common exomes 78,832/1,385,326 · genomes 12,841/151,944 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	16.2%	6
South Asian	9.38%	11
Finnishnot grpmax-eligible	7.98%	13
East Asian	7.86%	13
Ashkenazi Jewishnot grpmax-eligible	7.19%	14
Remaining individualsnot grpmax-eligible	6.43%	16
Middle Eastern	6.33%	16
European (non-Finnish)	4.96%	20
Admixed American	3.67%	27
Amishnot grpmax-eligible	2.74%	36

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.Gly980Arg
Coding: c.2938G>A
MANE Select: NM_182706
dbSNP: rs11542374
Type: single nucleotide variant
Location: chr8:143804639 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB
Residue 980: 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-gly980arg (accessed [today's date]).

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