Is ASB10 p.Val359Ile (c.1075G>A) pathogenic?

ASB10 p.Val359Ile (c.1075G>A) is classified Benign in ASB10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-08). AlphaMissense: likely benign (0.1493); Common (popmax 6.86%, sas) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about ASB10 p.Val359Ile (c.1075G>A)?

AlphaMissense predicts likely benign (score 0.1493) — an in-silico prediction, not a clinical call.

ASB10 p.Val359Ile

Q: How common is ASB10 p.Val359Ile (c.1075G>A) in the general population?

ASB10 p.Val359Ile (c.1075G>A) is common (popmax 6.86%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1075G>A · rs201566253 · VCV1228005

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1493 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.86%, sas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1493	likely benign
REVEL	0.175	moderately benign-leaning
SaProt	LLR -7.74	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 3.9	GERP -0.6, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 11 kb · p 0.61 · regional, not allelic
Overall
CADD	16.41	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.86% South Asian · 5,997/87,456 alleles

Filtering AF 6.71% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.65%

Overall 0.417% 6,541/1,567,696 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	6.86%	15
Remaining individualsnot grpmax-eligible	0.475%	210
Middle Eastern	0.179%	558
East Asian	0.0683%	1,463
African / African-American	0.0283%	3,530
European (non-Finnish)	0.0164%	6,093
Finnishnot grpmax-eligible	0.00827%	12,092
Admixed American	0.0071%	14,081

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: ASB10
Protein: p.Val359Ile
Coding: c.1075G>A
MANE Select: NM_001142459
dbSNP: rs201566253
Type: single nucleotide variant
Location: chr7:151180968 (GRCh38)
Gene constraint: LOEUF 1.634 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.98

Full ASB10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB10 p.Arg138Trp Uncertain significance ★★ ⚠ same type
ASB10 p.Arg434Cys Uncertain significance ★★ ⚠ same type
ASB10 p.Leu455Ile Uncertain significance ★★ ⚠ same type
ASB10 p.Phe416Leu Uncertain significance ★★ ⚠ same type
ASB10 p.Pro31Thr Uncertain significance ★★ ⚠ same type
ASB10 p.Pro346Ser Uncertain significance ★★ ⚠ same type
ASB10 p.Pro422Arg Uncertain significance ★★ ⚠ same type
ASB10 p.Pro451Leu 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/asb10-p-val359ile (accessed [today's date]).

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