Is ASB4 p.Glu116Lys (c.346G>A) pathogenic?

ASB4 p.Glu116Lys (c.346G>A) is classified Uncertain significance in ASB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-15). AlphaMissense: likely pathogenic (0.612); Rare (popmax 0.11%, sas).

How common is ASB4 p.Glu116Lys (c.346G>A) in the general population?

ASB4 p.Glu116Lys (c.346G>A) is rare (popmax 0.11%, sas) (gnomAD).

What do computational predictors say about ASB4 p.Glu116Lys (c.346G>A)?

AlphaMissense predicts likely pathogenic (score 0.612) — an in-silico prediction, not a clinical call.

ASB4 p.Glu116Lys

c.346G>A · VCV4152559

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.612 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.11%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.612	likely pathogenic
REVEL	0.231	benign-leaning
SaProt	LLR -7.16	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2.3, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 52 kb · p 0.19 · regional, not allelic
Overall
CADD	23.8	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 0.11% South Asian · 100/91,080 alleles

Filtering AF 0.0923% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0858%

Overall 0.00774% 125/1,614,132 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.11%	911
Middle Eastern	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.0032%	31,253
East Asian	0.00223%	44,868
European (non-Finnish)	0.00144%	69,413

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.Glu116Lys
Coding: c.346G>A
MANE Select: NM_016116
Type: single nucleotide variant
Location: chr7:95495916 (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-glu116lys (accessed [today's date]).

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