Is CABS1 p.Ala295Asp (c.884C>A) pathogenic?

CABS1 p.Ala295Asp (c.884C>A) is classified Uncertain significance in CABS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-10). AlphaMissense: likely benign (0.1396); Very rare (popmax 0.00017%, nfe).

How common is CABS1 p.Ala295Asp (c.884C>A) in the general population?

CABS1 p.Ala295Asp (c.884C>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about CABS1 p.Ala295Asp (c.884C>A)?

AlphaMissense predicts likely benign (score 0.1396) — an in-silico prediction, not a clinical call.

CABS1 p.Ala295Asp

c.884C>A · rs1269016157 · VCV3136262

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1396 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1396	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -5.50	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 0.044	GERP -1.6
Regional constraint	o/e 1.08	unconstrained · MANE · 1,184 bp · p 0.097 · regional, not allelic
Overall
CADD	5.457	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 0.00017% European (non-Finnish) · 2/1,179,710 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,414 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.Ala295Asp
Coding: c.884C>A
MANE Select: NM_033122
dbSNP: rs1269016157
Type: single nucleotide variant
Location: chr4:70335923 (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.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
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-ala295asp (accessed [today's date]).

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