Is ASCL4 p.Glu168Gln (c.502G>C) pathogenic?

ASCL4 p.Glu168Gln (c.502G>C) is classified Uncertain significance in ASCL4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). Ultra-rare (popmax 0.0626%, afr).

How common is ASCL4 p.Glu168Gln (c.502G>C) in the general population?

ASCL4 p.Glu168Gln (c.502G>C) is ultra-rare (popmax 0.0626%, afr) (gnomAD).

ASCL4 p.Glu168Gln

c.502G>C · VCV3435800

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0626%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.372	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.48, phastCons 1
Regional constraint	o/e 1.28	unconstrained · MANE · 515 bp · p 5.2e-06 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0626% African / African-American · 42/67,114 alleles

Filtering AF 0.0475% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0423%

Overall 0.0029% 42/1,448,536 alleles · ultra-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: ASCL4
Protein: p.Glu168Gln
Coding: c.502G>C
MANE Select: NM_203436
Type: single nucleotide variant
Location: chr12:107775720 (GRCh38)
Gene constraint: LOEUF 1.921 · pLI 0.13 (gnomAD)
Structure: AlphaFold pLDDT 71.48
Residue 168: the 'disordered' region

Full ASCL4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASCL4 p.Ala141Thr Uncertain significance ★ same type
ASCL4 p.Ala157Ser Uncertain significance ★ same type
ASCL4 p.Ala160Val Uncertain significance ★ same type
ASCL4 p.Ala50Glu Uncertain significance ★ same type
ASCL4 p.Ala68Thr Uncertain significance ★ same type
ASCL4 p.Arg115Cys Uncertain significance ★ same type
ASCL4 p.Arg32Gln Uncertain significance ★ same type
ASCL4 p.Arg33Gly 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/ascl4-p-glu168gln (accessed [today's date]).

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