Is CABS1 p.Asp381Gly (c.1142A>G) pathogenic?

CABS1 p.Asp381Gly (c.1142A>G) is classified Likely benign in CABS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: likely benign (0.0422); Very rare (popmax 0.00334%, amr).

How common is CABS1 p.Asp381Gly (c.1142A>G) in the general population?

CABS1 p.Asp381Gly (c.1142A>G) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about CABS1 p.Asp381Gly (c.1142A>G)?

AlphaMissense predicts likely benign (score 0.0422) — an in-silico prediction, not a clinical call.

CABS1 p.Asp381Gly

c.1142A>G · rs201451430 · VCV3136255

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0422 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0422	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -7.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.48	donor gain · deltas
Constraint at this position
Conservation	phyloP 1.8	GERP -1.1, phastCons 0.89
Regional constraint	o/e 1.08	unconstrained · MANE · 1,184 bp · p 0.097 · regional, not allelic
Overall
CADD	14.14	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 0.00334% Admixed American · 2/59,868 alleles

Filtering AF 0.000554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000434% 7/1,612,680 alleles · very rare exomes 5/1,460,548 · genomes 2/152,132 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,934
African / African-American	0.00133%	74,922
South Asian	0.0011%	90,964
European (non-Finnish)	0.000254%	393,079

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: CABS1
Protein: p.Asp381Gly
Coding: c.1142A>G
MANE Select: NM_033122
dbSNP: rs201451430
Type: single nucleotide variant
Location: chr4:70336181 (GRCh38)
Gene constraint: LOEUF 1.863 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 40.00

Full CABS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CABS1 p.Thr15Ala Benign ★★ same type
CABS1 p.Ala204Ser Uncertain significance ★ ⚠ same type
CABS1 p.Ala295Asp Uncertain significance ★ ⚠ same type
CABS1 p.Ala2Val Uncertain significance ★ ⚠ same type
CABS1 p.Ala327Glu Uncertain significance ★ ⚠ same type
CABS1 p.Ala330Thr Uncertain significance ★ ⚠ same type
CABS1 p.Arg181Gly Uncertain significance ★ ⚠ same type
CABS1 p.Asn348Asp Uncertain significance ★ ⚠ 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/cabs1-p-asp381gly (accessed [today's date]).

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