Is ASB4 p.Val44Met (c.130G>A) pathogenic?

ASB4 p.Val44Met (c.130G>A) is classified Uncertain significance in ASB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-01). AlphaMissense: likely pathogenic (0.7978); Very rare (popmax 0.00246%, nfe).

How common is ASB4 p.Val44Met (c.130G>A) in the general population?

ASB4 p.Val44Met (c.130G>A) is very rare (popmax 0.00246%, nfe) (gnomAD).

What do computational predictors say about ASB4 p.Val44Met (c.130G>A)?

AlphaMissense predicts likely pathogenic (score 0.7978) — an in-silico prediction, not a clinical call.

ASB4 p.Val44Met

c.130G>A · VCV4152607

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7978 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7978	likely pathogenic
REVEL	0.234	benign-leaning
SaProt	LLR -12.77	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 52 kb · p 0.19 · regional, not allelic
Overall
CADD	27.8	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 0.00246% European (non-Finnish) · 29/1,180,010 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00204% 33/1,614,124 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00469%	21,339
European (non-Finnish)grpmax	0.00246%	40,690
Remaining individualsnot grpmax-eligible	0.0016%	62,508

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ASB4
Protein: p.Val44Met
Coding: c.130G>A
MANE Select: NM_016116
Type: single nucleotide variant
Location: chr7:95486101 (GRCh38)
Gene constraint: LOEUF 1.226 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.69

Full ASB4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASB4 p.Ala13Thr Uncertain significance ★ ⚠ same type
ASB4 p.Ala156Ser Uncertain significance ★ ⚠ same type
ASB4 p.Ala182Thr Uncertain significance ★ ⚠ same type
ASB4 p.Ala206Val Uncertain significance ★ ⚠ same type
ASB4 p.Ala35Ser Uncertain significance ★ ⚠ same type
ASB4 p.Ala58Thr Uncertain significance ★ ⚠ same type
ASB4 p.Ala6Asp Uncertain significance ★ ⚠ same type
ASB4 p.Arg236Cys 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/asb4-p-val44met (accessed [today's date]).

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