Is ABTB2 p.Pro564Ser (c.1690C>T) pathogenic?

ABTB2 p.Pro564Ser (c.1690C>T) is classified Uncertain significance in ABTB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely benign (0.2456); Very rare (popmax 0.00659%, sas).

How common is ABTB2 p.Pro564Ser (c.1690C>T) in the general population?

ABTB2 p.Pro564Ser (c.1690C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about ABTB2 p.Pro564Ser (c.1690C>T)?

AlphaMissense predicts likely benign (score 0.2456) — an in-silico prediction, not a clinical call.

ABTB2 p.Pro564Ser

c.1690C>T · rs762551459 · VCV2616334

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2456 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2456	likely benign
REVEL	0.294	indeterminate
SaProt	LLR -7.68	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 205 kb · p 0.0006 · regional, not allelic
Overall
CADD	27.0	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 0.00659% South Asian · 6/90,984 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.000372% 6/1,613,584 alleles · very rare exomes 5/1,461,268 · genomes 1/152,316 · joint denominator

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: ABTB2
Protein: p.Pro564Ser
Coding: c.1690C>T
MANE Select: NM_145804
dbSNP: rs762551459
Type: single nucleotide variant
Location: chr11:34167324 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.05

Full ABTB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABTB2 p.Ala122Pro Uncertain significance ★ ⚠ same type
ABTB2 p.Ala129Val Uncertain significance ★ ⚠ same type
ABTB2 p.Ala181Val Uncertain significance ★ ⚠ same type
ABTB2 p.Ala248Thr Uncertain significance ★ ⚠ same type
ABTB2 p.Ala257Thr Uncertain significance ★ ⚠ same type
ABTB2 p.Ala293Thr Uncertain significance ★ ⚠ same type
ABTB2 p.Ala301Pro Uncertain significance ★ ⚠ same type
ABTB2 p.Ala301Thr 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/abtb2-p-pro564ser (accessed [today's date]).

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