Is SCRIB p.Pro985= (c.2955G>A) pathogenic?

SCRIB p.Pro985= (c.2955G>A) is classified Likely benign in SCRIB (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-23). Very rare (popmax 0.00599%, amr); Associated with SCRIB-related disorder.

What condition is associated with SCRIB p.Pro985= (c.2955G>A)?

SCRIB p.Pro985= (c.2955G>A) is associated with SCRIB-related disorder (ClinVar).

How common is SCRIB p.Pro985= (c.2955G>A) in the general population?

SCRIB p.Pro985= (c.2955G>A) is very rare (popmax 0.00599%, amr) (gnomAD).

SCRIB p.Pro985=

c.2955G>A · rs782285085 · VCV3048288

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00599%, amr)

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 -1.1	GERP -2.6
Overall
CADD	1.142	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00599% Admixed American · 3/50,070 alleles

Filtering AF 0.00159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000841%

Overall 0.000787% 12/1,525,404 alleles · very rare exomes 12/1,373,262 · genomes 0/152,142 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00599%	16,690
South Asian	0.00381%	26,276
Remaining individualsnot grpmax-eligible	0.0017%	58,736
European (non-Finnish)	0.000439%	227,585

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.Pro985=
Coding: c.2955G>A
MANE Select: NM_182706
dbSNP: rs782285085
Type: single nucleotide variant
Location: chr8:143804622 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB
Residue 985: 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.Pro985Arg Uncertain significance ★ ⚠ same residue
SCRIB p.Pro985Leu Likely benign ★ 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

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-pro985 (accessed [today's date]).

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