Is CABS1 p.Ala2Val (c.5C>T) pathogenic?

CABS1 p.Ala2Val (c.5C>T) is classified Uncertain significance in CABS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-07). AlphaMissense: likely pathogenic (0.6309); Absent from gnomAD v4.1.

How common is CABS1 p.Ala2Val (c.5C>T) in the general population?

CABS1 p.Ala2Val (c.5C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CABS1 p.Ala2Val (c.5C>T)?

AlphaMissense predicts likely pathogenic (score 0.6309) — an in-silico prediction, not a clinical call.

CABS1 p.Ala2Val

c.5C>T · VCV3483882

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6309 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6309	likely pathogenic · top 3% in CABS1
REVEL	0.126	moderately benign-leaning
SaProt	LLR -6.25	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 2, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 1,184 bp · p 0.097 · regional, not allelic
Overall
CADD	23.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CABS1
Protein: p.Ala2Val
Coding: c.5C>T
MANE Select: NM_033122
Type: single nucleotide variant
Location: chr4:70335044 (GRCh38)
Gene constraint: LOEUF 1.863 · pLI 0.18 (gnomAD)
Structure: AlphaFold pLDDT 40.00
Residue 2: the 'disordered' region

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.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
CABS1 p.Asp288Gly 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-ala2val (accessed [today's date]).

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