Is ASB4 p.Glu305Lys (c.913G>A) pathogenic?

ASB4 p.Glu305Lys (c.913G>A) is classified Uncertain significance in ASB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-20). AlphaMissense: ambiguous (0.4218); Very rare (popmax 0.00666%, amr).

How common is ASB4 p.Glu305Lys (c.913G>A) in the general population?

ASB4 p.Glu305Lys (c.913G>A) is very rare (popmax 0.00666%, amr) (gnomAD).

What do computational predictors say about ASB4 p.Glu305Lys (c.913G>A)?

AlphaMissense predicts ambiguous (score 0.4218) — an in-silico prediction, not a clinical call.

ASB4 p.Glu305Lys

c.913G>A · rs775399940 · VCV2268057

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4218 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00666%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4218	ambiguous
REVEL	0.15	moderately benign-leaning
SaProt	LLR -11.03	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.3, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 52 kb · p 0.19 · regional, not allelic
Overall
CADD	28.4	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 0.00666% Admixed American · 4/60,022 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000342% 5/1,461,890 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00666%	15,006
European (non-Finnish)	8.47e-05%	1,180,012

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.Glu305Lys
Coding: c.913G>A
MANE Select: NM_016116
dbSNP: rs775399940
Type: single nucleotide variant
Location: chr7:95528238 (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-glu305lys (accessed [today's date]).

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