Is SCRIB p.Asp402Asn (c.1204G>A) pathogenic?

SCRIB p.Asp402Asn (c.1204G>A) is classified Uncertain significance in SCRIB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: likely benign (0.2398); Ultra-rare (popmax 0.0813%, afr).

How common is SCRIB p.Asp402Asn (c.1204G>A) in the general population?

SCRIB p.Asp402Asn (c.1204G>A) is ultra-rare (popmax 0.0813%, afr) (gnomAD).

What do computational predictors say about SCRIB p.Asp402Asn (c.1204G>A)?

AlphaMissense predicts likely benign (score 0.2398) — an in-silico prediction, not a clinical call.

SCRIB p.Asp402Asn

c.1204G>A · rs370180598 · VCV3158663

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2398 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0813%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2398	likely benign
REVEL	0.363	indeterminate
SaProt	LLR -8.22	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP -1.9, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 4,447 bp · p 0.0026 · regional, not allelic
Overall
CADD	23.8	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 0.0813% African / African-American · 61/75,038 alleles

Filtering AF 0.0649% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.059%

Overall 0.00434% 70/1,611,772 alleles · ultra-rare exomes 37/1,459,414 · genomes 33/152,358 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0813%	1,230
Admixed American	0.00334%	29,940
Remaining individualsnot grpmax-eligible	0.00321%	31,185
South Asian	0.0022%	45,460
European (non-Finnish)	0.000254%	393,178

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.Asp402Asn
Coding: c.1204G>A
MANE Select: NM_182706
dbSNP: rs370180598
Type: single nucleotide variant
Location: chr8:143810975 (GRCh38)
Gene constraint: LOEUF 0.684 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 52.33 · 42 PDB
Residue 402: 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

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-asp402asn (accessed [today's date]).

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