Is ASB8 p.Arg260Pro (c.779G>C) pathogenic?

ASB8 p.Arg260Pro (c.779G>C) is classified Uncertain significance in ASB8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: likely pathogenic (0.6415); Very rare (popmax 0.000339%, nfe).

How common is ASB8 p.Arg260Pro (c.779G>C) in the general population?

ASB8 p.Arg260Pro (c.779G>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about ASB8 p.Arg260Pro (c.779G>C)?

AlphaMissense predicts likely pathogenic (score 0.6415) — an in-silico prediction, not a clinical call.

ASB8 p.Arg260Pro

c.779G>C · rs75959434 · VCV3130207

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6415 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6415	likely pathogenic
REVEL	0.192	benign-leaning
SaProt	LLR -14.17	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.38	GERP -1.3, phastCons 0.03
Regional constraint	o/e 0.82	unconstrained · MANE · 4,127 bp · p 0.00087 · regional, not allelic
Overall
CADD	16.49	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,179,778 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,802 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: ASB8
Protein: p.Arg260Pro
Coding: c.779G>C
MANE Select: NM_024095
dbSNP: rs75959434
Type: single nucleotide variant
Location: chr12:48149454 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.41 · 5 PDB
Residue 260: the socs box domain

Full ASB8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB8 p.Ala125Glu Uncertain significance ★ ⚠ same type
ASB8 p.Ala142Thr Uncertain significance ★ ⚠ same type
ASB8 p.Ala175Thr Uncertain significance ★ ⚠ same type
ASB8 p.Ala254Thr Uncertain significance ★ ⚠ same type
ASB8 p.Ala278Pro Uncertain significance ★ ⚠ same type
ASB8 p.Arg135Gln Uncertain significance ★ ⚠ same type
ASB8 p.Arg190His Uncertain significance ★ ⚠ same type
ASB8 p.Arg21Cys 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/asb8-p-arg260pro (accessed [today's date]).

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