Is ASCL3 p.Ser89Phe (c.266C>T) pathogenic?

ASCL3 p.Ser89Phe (c.266C>T) is classified Uncertain significance in ASCL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-20). Very rare (popmax 0.000169%, nfe).

How common is ASCL3 p.Ser89Phe (c.266C>T) in the general population?

ASCL3 p.Ser89Phe (c.266C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

ASCL3 p.Ser89Phe

c.266C>T · VCV3435760

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.504	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 542 bp · p 0.35 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,998 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,858 alleles · very rare

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: ASCL3
Protein: p.Ser89Phe
Coding: c.266C>T
MANE Select: NM_020646
Type: single nucleotide variant
Location: chr11:8937896 (GRCh38)
Gene constraint: LOEUF 1.504 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 69.74

Full ASCL3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASCL3 p.Ala114Thr Uncertain significance ★ same type
ASCL3 p.Ala138Glu Uncertain significance ★ same type
ASCL3 p.Ala154Thr Uncertain significance ★ same type
ASCL3 p.Ala93Gly Uncertain significance ★ same type
ASCL3 p.Arg101Trp Uncertain significance ★ same type
ASCL3 p.Arg105Gln Uncertain significance ★ same type
ASCL3 p.Arg117Cys Uncertain significance ★ same type
ASCL3 p.Arg22Cys 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/ascl3-p-ser89phe (accessed [today's date]).

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