Is ASB14 p.Arg565Ser (c.1693C>A) pathogenic?

ASB14 p.Arg565Ser (c.1693C>A) is classified Uncertain significance in ASB14 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). AlphaMissense: likely benign (0.1564); Ultra-rare (popmax 0.0126%, nfe).

How common is ASB14 p.Arg565Ser (c.1693C>A) in the general population?

ASB14 p.Arg565Ser (c.1693C>A) is ultra-rare (popmax 0.0126%, nfe) (gnomAD).

What do computational predictors say about ASB14 p.Arg565Ser (c.1693C>A)?

AlphaMissense predicts likely benign (score 0.1564) — an in-silico prediction, not a clinical call.

ASB14 p.Arg565Ser

c.1693C>A · rs147845490 · VCV2388792

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1564 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0126%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1564	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -7.31	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 3	GERP -0.37, phastCons 0.99
Regional constraint	o/e 1.02	unconstrained · MANE · 15 kb · p 0.61 · regional, not allelic
Overall
CADD	22.1	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 0.0126% European (non-Finnish) · 149/1,179,676 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0103%

Overall 0.00961% 155/1,613,622 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0126%	7,917
Remaining individualsnot grpmax-eligible	0.0096%	10,413

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.Arg565Ser
Coding: c.1693C>A
MANE Select: NM_001142733
dbSNP: rs147845490
Type: single nucleotide variant
Location: chr3:57276621 (GRCh38)
Gene constraint: LOEUF 1.35 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.24
Residue 565: the socs box domain

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

Similar variants

ASB14 p.Arg565Cys Uncertain significance ★ ⚠ same residue
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

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-arg565ser (accessed [today's date]).

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