Is SCRIB p.Glu1632Gln (c.4894G>C) pathogenic?

SCRIB p.Glu1632Gln (c.4894G>C) is classified Uncertain significance in SCRIB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-23). AlphaMissense: likely benign (0.1231); Ultra-rare (popmax 0.0726%, eas).

How common is SCRIB p.Glu1632Gln (c.4894G>C) in the general population?

SCRIB p.Glu1632Gln (c.4894G>C) is ultra-rare (popmax 0.0726%, eas) (gnomAD).

What do computational predictors say about SCRIB p.Glu1632Gln (c.4894G>C)?

AlphaMissense predicts likely benign (score 0.1231) — an in-silico prediction, not a clinical call.

SCRIB p.Glu1632Gln

c.4894G>C · VCV3793331

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1231 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0726%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1231	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.4, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 20 kb · p 9.1e-08 · regional, not allelic
Overall
CADD	23.3	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 is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E1607Q vs ClinVar E1632Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0726% East Asian · 30/41,308 alleles

Filtering AF 0.0523% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0453%

Overall 0.00208% 31/1,488,550 alleles · ultra-rare exomes 27/1,336,222 · genomes 4/152,328 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0726%	1,377
Remaining individualsnot grpmax-eligible	0.00175%	57,202

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.Glu1632Gln
Coding: c.4894G>C
MANE Select: NM_182706
Type: single nucleotide variant
Location: chr8:143791237 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB

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

Similar variants

SCRIB c.3120+10C>G Benign/Likely benign ★★ same type
SCRIB c.504-9C>T Benign ★★ same type
SCRIB p.Ala1488= Likely benign ★★ same type
SCRIB p.Arg492= Benign ★★ same type
SCRIB p.Asn647= Benign/Likely benign ★★ same type
SCRIB p.Leu254= Benign ★★ same type
SCRIB p.Phe571= Benign ★★ same type
SCRIB p.Pro1343= Benign ★★ same type

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-glu1632gln (accessed [today's date]).

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