Is ASB14 p.Arg532Pro (c.1595G>C) pathogenic?

ASB14 p.Arg532Pro (c.1595G>C) is classified Uncertain significance in ASB14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-07). AlphaMissense: ambiguous (0.4751); Ultra-rare (popmax 0.0643%, afr).

How common is ASB14 p.Arg532Pro (c.1595G>C) in the general population?

ASB14 p.Arg532Pro (c.1595G>C) is ultra-rare (popmax 0.0643%, afr) (gnomAD).

What do computational predictors say about ASB14 p.Arg532Pro (c.1595G>C)?

AlphaMissense predicts ambiguous (score 0.4751) — an in-silico prediction, not a clinical call.

ASB14 p.Arg532Pro

c.1595G>C · VCV3317237

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4751 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0643%, afr)

Computational evidence

Protein change
AlphaMissense	0.4751	ambiguous
REVEL	0.328	indeterminate
SaProt	LLR -10.99	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 15 kb · p 0.61 · regional, not allelic
Overall
CADD	26.6	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 0.0643% African / African-American · 48/74,616 alleles

Filtering AF 0.0498% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0446%

Overall 0.00305% 49/1,607,154 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0643%	1,554
Remaining individualsnot grpmax-eligible	0.00161%	62,260

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: ASB14
Protein: p.Arg532Pro
Coding: c.1595G>C
MANE Select: NM_001142733
Type: single nucleotide variant
Location: chr3:57276719 (GRCh38)
Gene constraint: LOEUF 1.35 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.24
Residue 532: the socs box domain

Full ASB14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB14 p.Ala104Val Uncertain significance ★ ⚠ same type
ASB14 p.Ala221Thr Uncertain significance ★ ⚠ same type
ASB14 p.Ala257Thr Uncertain significance ★ ⚠ same type
ASB14 p.Ala297Gly Uncertain significance ★ ⚠ same type
ASB14 p.Ala33Ser Uncertain significance ★ ⚠ same type
ASB14 p.Ala363Pro Uncertain significance ★ ⚠ same type
ASB14 p.Ala378Val Uncertain significance ★ ⚠ same type
ASB14 p.Ala48Thr 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/asb14-p-arg532pro (accessed [today's date]).

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