Is ASB7 p.Ala45Val (c.134C>T) pathogenic?

ASB7 p.Ala45Val (c.134C>T) is classified Uncertain significance in ASB7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-17). AlphaMissense: likely benign (0.2467); Very rare (popmax 0.00133%, afr).

How common is ASB7 p.Ala45Val (c.134C>T) in the general population?

ASB7 p.Ala45Val (c.134C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ASB7 p.Ala45Val (c.134C>T)?

AlphaMissense predicts likely benign (score 0.2467) — an in-silico prediction, not a clinical call.

ASB7 p.Ala45Val

c.134C>T · VCV4831241

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2467 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2467	likely benign
REVEL	0.198	benign-leaning
SaProt	LLR -6.64	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 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 36 kb · p 3.9e-29 · regional, not allelic
Overall
CADD	23.5	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 0.00133% African / African-American · 1/75,022 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000889% 13/1,461,756 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,022
European (non-Finnish)	0.00102%	98,325

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.Ala45Val
Coding: c.134C>T
MANE Select: NM_198243
Type: single nucleotide variant
Location: chr15:100612350 (GRCh38)
Gene constraint: LOEUF 0.277 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 92.09 · 1 PDB

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.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-ala45val (accessed [today's date]).

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