Is CABS1 p.Lys76Arg (c.227A>G) pathogenic?

CABS1 p.Lys76Arg (c.227A>G) is classified Likely benign in CABS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-29). AlphaMissense: likely benign (0.1071); Very rare (popmax 0.000593%, nfe).

How common is CABS1 p.Lys76Arg (c.227A>G) in the general population?

CABS1 p.Lys76Arg (c.227A>G) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about CABS1 p.Lys76Arg (c.227A>G)?

AlphaMissense predicts likely benign (score 0.1071) — an in-silico prediction, not a clinical call.

CABS1 p.Lys76Arg

c.227A>G · rs773923155 · VCV3136257

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1071 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1071	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -7.53	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -0.96, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 1,184 bp · p 0.097 · regional, not allelic
Overall
CADD	11.38	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 0.000593% European (non-Finnish) · 7/1,179,846 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000434% 7/1,613,480 alleles · very rare

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.Lys76Arg
Coding: c.227A>G
MANE Select: NM_033122
dbSNP: rs773923155
Type: single nucleotide variant
Location: chr4:70335266 (GRCh38)
Gene constraint: LOEUF 1.863 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 40.00
Residue 76: a UniProt-annotated variant site (in)

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-lys76arg (accessed [today's date]).

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