Is ASB7 p.Val75Ile (c.223G>A) pathogenic?

ASB7 p.Val75Ile (c.223G>A) is classified Uncertain significance in ASB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely benign (0.0896); Very rare (popmax 0.0011%, sas).

How common is ASB7 p.Val75Ile (c.223G>A) in the general population?

ASB7 p.Val75Ile (c.223G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ASB7 p.Val75Ile (c.223G>A)?

AlphaMissense predicts likely benign (score 0.0896) — an in-silico prediction, not a clinical call.

ASB7 p.Val75Ile

c.223G>A · rs759632704 · VCV2492478

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0896 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0896	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -5.52	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 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 36 kb · p 3.9e-29 · regional, not allelic
Overall
CADD	21.9	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 0.0011% South Asian · 1/90,992 alleles

Overall 6.85e-05% 1/1,458,922 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: ASB7
Protein: p.Val75Ile
Coding: c.223G>A
MANE Select: NM_198243
dbSNP: rs759632704
Type: single nucleotide variant
Location: chr15:100629448 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.09 · 1 PDB
Residue 75: an α-helix

Full ASB7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB7 p.Ala71= Benign ★★ same type
ASB7 p.Leu233= Benign ★★ same type
ASB7 p.Leu297= Benign ★★ same type
ASB7 p.Ala45Val Uncertain significance ★ ⚠ same type
ASB7 p.Arg231Gln Uncertain significance ★ ⚠ same type
ASB7 p.Asn173Ser Uncertain significance ★ ⚠ same type
ASB7 p.Asp171His Uncertain significance ★ ⚠ same type
ASB7 p.Asp239Gly 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/asb7-p-val75ile (accessed [today's date]).

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