Is CABS1 p.Val207Ala (c.620T>C) pathogenic?

CABS1 p.Val207Ala (c.620T>C) is classified Uncertain significance in CABS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-30). AlphaMissense: likely benign (0.2061); Ultra-rare (popmax 0.0321%, afr).

How common is CABS1 p.Val207Ala (c.620T>C) in the general population?

CABS1 p.Val207Ala (c.620T>C) is ultra-rare (popmax 0.0321%, afr) (gnomAD).

What do computational predictors say about CABS1 p.Val207Ala (c.620T>C)?

AlphaMissense predicts likely benign (score 0.2061) — an in-silico prediction, not a clinical call.

CABS1 p.Val207Ala

c.620T>C · rs756611138 · VCV2589222

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2061 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0321%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2061	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -6.57	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 -0.24	GERP -3.5
Regional constraint	o/e 1.08	unconstrained · MANE · 1,184 bp · p 0.097 · regional, not allelic
Overall
CADD	2.075	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 0.0321% African / African-American · 24/74,880 alleles

Filtering AF 0.022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0187%

Overall 0.00236% 38/1,613,462 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0321%	3,120
Admixed American	0.015%	6,652
Remaining individualsnot grpmax-eligible	0.00801%	12,490

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.Val207Ala
Coding: c.620T>C
MANE Select: NM_033122
dbSNP: rs756611138
Type: single nucleotide variant
Location: chr4:70335659 (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-val207ala (accessed [today's date]).

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