Is ASB17 p.Ile18Val (c.52A>G) pathogenic?

ASB17 p.Ile18Val (c.52A>G) is classified Uncertain significance in ASB17 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-17). AlphaMissense: likely benign (0.1002); Very rare (popmax 8.48e-05%, nfe).

How common is ASB17 p.Ile18Val (c.52A>G) in the general population?

ASB17 p.Ile18Val (c.52A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about ASB17 p.Ile18Val (c.52A>G)?

AlphaMissense predicts likely benign (score 0.1002) — an in-silico prediction, not a clinical call.

ASB17 p.Ile18Val

c.52A>G · VCV3788577

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1002 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1002	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -5.61	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 2.1	GERP -0.79, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 13 kb · p 0.5 · regional, not allelic
Overall
CADD	11.49	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 8.48e-05% European (non-Finnish) · 1/1,179,766 alleles

Overall 6.84e-05% 1/1,461,316 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: ASB17
Protein: p.Ile18Val
Coding: c.52A>G
MANE Select: NM_080868
Type: single nucleotide variant
Location: chr1:75932240 (GRCh38)
Gene constraint: LOEUF 1.363 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.18

Full ASB17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB17 p.Ala65Thr Uncertain significance ★ ⚠ same type
ASB17 p.Arg286Cys Uncertain significance ★ ⚠ same type
ASB17 p.Arg46Lys Uncertain significance ★ ⚠ same type
ASB17 p.Asn128Lys Uncertain significance ★ ⚠ same type
ASB17 p.Asp197Glu Uncertain significance ★ ⚠ same type
ASB17 p.Asp59Asn Uncertain significance ★ ⚠ same type
ASB17 p.Asp64Glu Uncertain significance ★ ⚠ same type
ASB17 p.Cys260Ser 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/asb17-p-ile18val (accessed [today's date]).

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