Is ASB10 p.Val86Ile (c.256G>A) pathogenic?

ASB10 p.Val86Ile (c.256G>A) is classified Uncertain significance in ASB10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-14). AlphaMissense: likely benign (0.0737); Ultra-rare (popmax 0.011%, sas).

How common is ASB10 p.Val86Ile (c.256G>A) in the general population?

ASB10 p.Val86Ile (c.256G>A) is ultra-rare (popmax 0.011%, sas) (gnomAD).

What do computational predictors say about ASB10 p.Val86Ile (c.256G>A)?

AlphaMissense predicts likely benign (score 0.0737) — an in-silico prediction, not a clinical call.

ASB10 p.Val86Ile

c.256G>A · rs775064026 · VCV2195540

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0737 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0737	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -7.71	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 -5	GERP -2.4
Regional constraint	o/e 1.02	unconstrained · MANE · 11 kb · p 0.61 · regional, not allelic
Overall
CADD	0.202	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 0.011% South Asian · 10/91,030 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00453%

Overall 0.00205% 33/1,613,160 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.011%	9,103
African / African-American	0.00668%	14,980
East Asian	0.00223%	44,842
Admixed American	0.00167%	59,950
Remaining individualsnot grpmax-eligible	0.0016%	62,456
European (non-Finnish)	0.00127%	78,637

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.Val86Ile
Coding: c.256G>A
MANE Select: NM_001142459
dbSNP: rs775064026
Type: single nucleotide variant
Location: chr7:151186875 (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.Val86Ala Uncertain significance ★ ⚠ same residue
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

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-val86ile (accessed [today's date]).

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