Is ASB7 p.Leu233= (c.699A>G) pathogenic?

ASB7 p.Leu233= (c.699A>G) is classified Benign in ASB7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-16). Common (popmax 5.53%, afr) — too common for a highly-penetrant pathogenic allele.

ASB7 p.Leu233=

Q: How common is ASB7 p.Leu233= (c.699A>G) in the general population?

ASB7 p.Leu233= (c.699A>G) is common (popmax 5.53%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.699A>G · rs73483052 · VCV776947

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.53%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.7	GERP -3.4
Overall
CADD	2.991	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.53% African / African-American · 4,152/75,034 alleles

Filtering AF 5.39% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.34%

Overall 0.287% 4,634/1,614,190 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.53%	18
Remaining individualsnot grpmax-eligible	0.336%	298
Admixed American	0.333%	300
Middle Eastern	0.214%	466
South Asian	0.00769%	13,012
European (non-Finnish)	0.00432%	23,138
East Asian	0.00223%	44,882

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.Leu233=
Coding: c.699A>G
MANE Select: NM_198243
dbSNP: rs73483052
Type: single nucleotide variant
Location: chr15:100629924 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.09 · 1 PDB
Residue 233: 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.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
ASB7 p.Asp316Gly 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-leu233 (accessed [today's date]).

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