Is CABIN1 p.Pro2091Ser (c.6271C>T) pathogenic?

CABIN1 p.Pro2091Ser (c.6271C>T) is classified Uncertain significance in CABIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). AlphaMissense: likely benign (0.0657); Rare (popmax 0.103%, afr).

How common is CABIN1 p.Pro2091Ser (c.6271C>T) in the general population?

CABIN1 p.Pro2091Ser (c.6271C>T) is rare (popmax 0.103%, afr) (gnomAD).

What do computational predictors say about CABIN1 p.Pro2091Ser (c.6271C>T)?

AlphaMissense predicts likely benign (score 0.0657) — an in-silico prediction, not a clinical call.

CABIN1 p.Pro2091Ser

c.6271C>T · VCV3826485

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0657 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.103%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0657	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -6.73	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 0.078	GERP -2.9
Regional constraint	o/e 0.92	unconstrained · MANE · 13 kb · p 0.032 · regional, not allelic
Overall
CADD	7.072	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 0.103% African / African-American · 77/74,728 alleles

Filtering AF 0.0844% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0776%

Overall 0.00507% 81/1,598,558 alleles · rare exomes 39/1,446,308 · genomes 42/152,250 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.103%	970
Remaining individualsnot grpmax-eligible	0.00486%	20,559
European (non-Finnish)	8.55e-05%	1,169,738

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: CABIN1
Protein: p.Pro2091Ser
Coding: c.6271C>T
MANE Select: NM_012295
Type: single nucleotide variant
Location: chr22:24177569 (GRCh38)
Gene constraint: LOEUF 0.661 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.03 · 1 PDB
Residue 2091: the 'disordered' region

Full CABIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CABIN1 p.Arg51Trp Uncertain significance ★★ ⚠ same type
CABIN1 p.Glu256Lys Uncertain significance ★★ ⚠ same type
CABIN1 p.Pro1981Leu Uncertain significance ★★ ⚠ same type
CABIN1 p.Ser222Leu Uncertain significance ★★ ⚠ same type
CABIN1 c.1262+10A>G Benign/Likely benign ★★ same type
CABIN1 c.1262+62= Benign ★★ same type
CABIN1 c.2748+37= Benign ★★ same type
CABIN1 c.2911-29= Benign ★★ 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/cabin1-p-pro2091ser (accessed [today's date]).

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