Is ASB6 p.Ile109Val (c.325A>G) pathogenic?

ASB6 p.Ile109Val (c.325A>G) is classified Uncertain significance in ASB6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.1036); Ultra-rare (popmax 0.0253%, afr).

How common is ASB6 p.Ile109Val (c.325A>G) in the general population?

ASB6 p.Ile109Val (c.325A>G) is ultra-rare (popmax 0.0253%, afr) (gnomAD).

What do computational predictors say about ASB6 p.Ile109Val (c.325A>G)?

AlphaMissense predicts likely benign (score 0.1036) — an in-silico prediction, not a clinical call.

ASB6 p.Ile109Val

c.325A>G · VCV4152788

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1036 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1036	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -5.24	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 6.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,206 bp · p 0.085 · regional, not allelic
Overall
CADD	18.33	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 0.0253% African / African-American · 19/75,064 alleles

Filtering AF 0.0165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00211% 34/1,613,748 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0253%	3,951
Admixed American	0.0167%	6,001
Remaining individualsnot grpmax-eligible	0.0016%	62,498
European (non-Finnish)	0.000339%	294,939

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: ASB6
Protein: p.Ile109Val
Coding: c.325A>G
MANE Select: NM_017873
Type: single nucleotide variant
Location: chr9:129639479 (GRCh38)
Gene constraint: LOEUF 1.225 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.02

Full ASB6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB6 p.Ile109Thr Uncertain significance ★ ⚠ same residue
ASB6 p.Val225= Likely benign ★★ same type
ASB6 p.Ala167Thr Uncertain significance ★ ⚠ same type
ASB6 p.Ala286Thr Uncertain significance ★ ⚠ same type
ASB6 p.Ala355Val Uncertain significance ★ ⚠ same type
ASB6 p.Ala43Ser Uncertain significance ★ ⚠ same type
ASB6 p.Ala72Thr Uncertain significance ★ ⚠ same type
ASB6 p.Ala77Val 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/asb6-p-ile109val (accessed [today's date]).

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