Is ASB4 p.Ala156Ser (c.466G>T) pathogenic?

ASB4 p.Ala156Ser (c.466G>T) is classified Uncertain significance in ASB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). AlphaMissense: likely benign (0.2535); Very rare (popmax 0.00212%, nfe).

How common is ASB4 p.Ala156Ser (c.466G>T) in the general population?

ASB4 p.Ala156Ser (c.466G>T) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about ASB4 p.Ala156Ser (c.466G>T)?

AlphaMissense predicts likely benign (score 0.2535) — an in-silico prediction, not a clinical call.

ASB4 p.Ala156Ser

c.466G>T · VCV3434914

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2535 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2535	likely benign
REVEL	0.44	indeterminate
SaProt	LLR -9.89	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 52 kb · p 0.19 · regional, not allelic
Overall
CADD	27.2	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 0.00212% European (non-Finnish) · 25/1,179,286 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00167% 27/1,613,044 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00212%	47,171
Admixed American	0.00167%	59,988
Remaining individualsnot grpmax-eligible	0.0016%	62,454

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.Ala156Ser
Coding: c.466G>T
MANE Select: NM_016116
Type: single nucleotide variant
Location: chr7:95496036 (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.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
ASB4 p.Arg299Cys 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-ala156ser (accessed [today's date]).

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