Is ASB2 p.Pro595Thr (c.1783C>A) pathogenic?

ASB2 p.Pro595Thr (c.1783C>A) is classified Uncertain significance in ASB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: ambiguous (0.3898); Absent from gnomAD v4.1.

How common is ASB2 p.Pro595Thr (c.1783C>A) in the general population?

ASB2 p.Pro595Thr (c.1783C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASB2 p.Pro595Thr (c.1783C>A)?

AlphaMissense predicts ambiguous (score 0.3898) — an in-silico prediction, not a clinical call.

ASB2 p.Pro595Thr

c.1783C>A · rs762879186 · VCV3130168

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3898 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3898	ambiguous
REVEL	0.109	moderately benign-leaning
SaProt	LLR -10.57	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 30 kb · p 0.18 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P547T vs ClinVar P595T) — verify the residue.

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: ASB2
Protein: p.Pro595Thr
Coding: c.1783C>A
MANE Select: NM_001202429
dbSNP: rs762879186
Type: single nucleotide variant
Location: chr14:93934781 (GRCh38)
Gene constraint: LOEUF 1.243 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.96
Residue 595: the socs box domain

Full ASB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB2 p.Ala132Thr Uncertain significance ★ ⚠ same type
ASB2 p.Ala196Thr Uncertain significance ★ same type
ASB2 p.Ala212Asp Uncertain significance ★ ⚠ same type
ASB2 p.Ala229Thr Uncertain significance ★ ⚠ same type
ASB2 p.Ala269Thr Uncertain significance ★ ⚠ same type
ASB2 p.Ala305Thr Uncertain significance ★ ⚠ same type
ASB2 p.Ala330Thr Uncertain significance ★ ⚠ same type
ASB2 p.Ala376Pro 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/asb2-p-pro595thr (accessed [today's date]).

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