Is ASB4 p.Phe48Ser (c.143T>C) pathogenic?

ASB4 p.Phe48Ser (c.143T>C) is classified Uncertain significance in ASB4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely pathogenic (0.9933); Ultra-rare (popmax 0.0307%, sas).

How common is ASB4 p.Phe48Ser (c.143T>C) in the general population?

ASB4 p.Phe48Ser (c.143T>C) is ultra-rare (popmax 0.0307%, sas) (gnomAD).

What do computational predictors say about ASB4 p.Phe48Ser (c.143T>C)?

AlphaMissense predicts likely pathogenic (score 0.9933) — an in-silico prediction, not a clinical call.

ASB4 p.Phe48Ser

c.143T>C · VCV4643400

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9933 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9933	likely pathogenic · top 3% in ASB4
REVEL	0.294	indeterminate
SaProt	LLR -12.38	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.5, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 52 kb · p 0.19 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0307% South Asian · 28/91,078 alleles

Filtering AF 0.0218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0188%

Overall 0.00192% 31/1,614,010 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0307%	3,253
European (non-Finnish)	0.000254%	393,338

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.Phe48Ser
Coding: c.143T>C
MANE Select: NM_016116
Type: single nucleotide variant
Location: chr7:95486114 (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-phe48ser (accessed [today's date]).

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