Is SCRIB p.Ser1179Asn (c.3536G>A) pathogenic?

SCRIB p.Ser1179Asn (c.3536G>A) is classified Uncertain significance in SCRIB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-08). AlphaMissense: likely benign (0.13); Ultra-rare (popmax 0.0673%, mid).

How common is SCRIB p.Ser1179Asn (c.3536G>A) in the general population?

SCRIB p.Ser1179Asn (c.3536G>A) is ultra-rare (popmax 0.0673%, mid) (gnomAD).

What do computational predictors say about SCRIB p.Ser1179Asn (c.3536G>A)?

AlphaMissense predicts likely benign (score 0.13) — an in-silico prediction, not a clinical call.

SCRIB p.Ser1179Asn

c.3536G>A · VCV4581397

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.13 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0673%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.13	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -8.69	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 -0.035	GERP 1.5
Regional constraint	o/e 1.13	unconstrained · MANE · 20 kb · p 9.1e-08 · regional, not allelic
Overall
CADD	9.148	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 0.0673% Middle Eastern · 4/5,942 alleles

Filtering AF 0.0229% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0155%

Overall 0.00194% 31/1,597,764 alleles · ultra-rare exomes 30/1,445,440 · genomes 1/152,324 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0673%	1,486
South Asian	0.0266%	3,764
Remaining individualsnot grpmax-eligible	0.00482%	20,733

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.Ser1179Asn
Coding: c.3536G>A
MANE Select: NM_182706
Type: single nucleotide variant
Location: chr8:143803450 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB
Residue 1179: 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

Similar variants

SCRIB p.Ser1179Gly Likely benign ★ same residue
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

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-ser1179asn (accessed [today's date]).

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