Is ASCL3 p.Pro176Arg (c.527C>G) pathogenic?

ASCL3 p.Pro176Arg (c.527C>G) is classified Uncertain significance in ASCL3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). Absent from gnomAD v4.1.

How common is ASCL3 p.Pro176Arg (c.527C>G) in the general population?

ASCL3 p.Pro176Arg (c.527C>G) is absent from gnomAD v4.1 (gnomAD).

ASCL3 p.Pro176Arg

c.527C>G · VCV3435751

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.41	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.64	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 5.9	GERP 1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 542 bp · p 0.35 · regional, not allelic
Overall
CADD	21.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ASCL3
Protein: p.Pro176Arg
Coding: c.527C>G
MANE Select: NM_020646
Type: single nucleotide variant
Location: chr11:8937635 (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-pro176arg (accessed [today's date]).

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